Human Development Days 1-4

Embryology-Early development/Organ system development
Once the sperm is anchored to the surface of the egg, the plasma membrane overlying the sperm and the
egg begin to fuse together—this is called sperm-binding.
Human development days 1-4 Now, the egg contains cortical granules which are like bags of enzymes, one being peroxidase.
When a sperm binds to the egg, calcium levels start rising within the egg’s cytosol.
Human development begins with fertilization, which is the moment when a sperm cell and an oocyte (or
egg cell) fuse to form a zygote, the seed of what will eventually grow into a human baby. This rise in the level of calcium signals the beginning of the cortical reaction, which is when the granules
fuse with the egg’s cell membrane, releasing enzymes into the space between the surface of the egg and the
During sex, semen containing about 200 million spermatozoa (or sperm) enters the vagina. fertilization envelope.
This seminal fluid is alkaline, which means it's capable of neutralizing acidic vaginal fluids. Like a chemistry experiment, the granule enzymes get mixed in with glycosaminoglycans, water, and
calcium ions, forming a gel-like barrier called the hyaline layer.
The sperm quickly make their way through the cervix and uterus and swim into the fallopian tubes, which
are also called the uterine tubes. This prevents polyspermy by ensuring that only one sperm can get in to fertilize the egg.
Eventually, these millions of sperm enter the ampulla of the uterine tube and then the infundibulum, an This isn’t always effective, of course, as you’ll see in the development of twins chapter later in the book.
opening which flowers out next to the ovary.
So, that’s how a single sperm out of hundreds of millions successfully enters the egg—those are about the
By this point, most of the 200 million sperm that entered the body during sex have died for numerous odds of winning a major lottery!
reasons: some got stuck in the vaginal mucus, others ended up lost in the cervix, and the rest were killed
and absorbed by the white blood cells. While this is all happening, the egg undergoes its own set of cell divisions called meiosis II, leaving one
polar body which has barely any cytoplasm, and soon undergoes apoptosis.
About a thousand lucky survivors are left to wait in the uterine tube for the egg to arrive.
The surviving daughter cell ultimately forms the mature female ovum, or egg.
As the sperm wait, they start to rub up against the walls of the uterine tube, and that helps them remove the
protective glycoprotein coat and plasma membrane covering the acrosome, a cap-like structure covering The nucleus of this egg is called the female pronucleus, and it contains 23 chromosomes.
what you might think of as the sperm’s head. This process is called capacitation.
Once our lottery-winning winning sperm has shed its sugary protein coat completely, it leaves that behind
Once these protective outer layers are gone, the sperm are able to secrete an enzyme called hyaluronidase on the egg’s surface and uses its tail and mitochondria to make one final short swim over to the female
which can break down hyaluronic acid, a major component of the extracellular matrix protecting the egg. pronucleus (the nucleus of the egg), settling down beside it.
Now, the egg is the largest cell in the human body, big and round, the size of a grain of sand. Once the sperm’s at rest, its tail and mitochondria detach and degenerate, and the nucleus expands a bit to
become the male pronucleus.
As you’ll soon see, it’s kind of like an onion, as it’s made up of many layers.
Like dancers on a stage, the male and female pronuclei slowly move toward each other in the center of the
The sperm trying to enter and fertilize this big egg are the smallest cells in the human body—about 1/30th egg.
the size of the egg—and they’re long and thin.
As they move together, a groove forms between them, and their individual nuclear envelopes dissolve.
The most intrepid sperm make their way past the extracellular matrix surrounding the egg to a deeper
layer called the corona radiata, which is made up of follicular cells. The pronuclei release their genetic information, merging into a single nucleus, leaving no barrier between
the male and female chromosomes.
The sperm then make their way through the corona radiata to the zona pellucida, another layer of
extracellular matrix made of glycoproteins, which protects the egg. Only about 500 sperm cells make it this A structure made of microtubules called the mitotic spindle forms across the diameter of this brand new
far! cell, and it weaves the chromosomes into complementary pairs, aligning them at the equator of the cell.
The zona pellucida is also called the jelly coat, since it’s a clear, jelly-like covering wrapped around the egg. Now that this new cell contains both maternal and paternal genetic information, it’s become diploid—a
zygote has formed!
The jelly coat/zona pellucida lies over another layer, this one made up of a protein called zona pellucida
sperm-binding protein 3, or ZP3 protein for short. This moment in embryonic development where there’s a single cell containing genetic information from
two different sources is called syngamy; it lasts just a few hours before the process of cell division begins.
As sperm close in on the zona pellucida, they undergo a process called the acrosome reaction, which
happens in two parts.
First, the sperm release acrosin, a hydrolytic enzyme that bores a hole in the jelly-like coating of the zona
Summary
pellucida.
After that, the sperm start assembling actin proteins, which fold out like a large protein crane, anchoring All right, as a quick recap… Fertilization occurs when a sperm successfully navigates through the vagina,
and binding the sperm to the ZP3 proteins. cervix, uterus, and uterine tubes to meet the egg.
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From there, it makes its way through the corona radiata, the zona pellucida, and the oocyte cell membrane,
to ultimately fuse with the egg.
The genetic materials contained within the nuclei of the sperm and egg combine to produce a brand new
diploid cell called a zygote.
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All right, as a quick recap… Just a few hours after its formation (around 1–2 days after initial fertilization),
the zygote undergoes a series of mitotic divisions, which lasts through days 2–4, before developing into a
blastocyst around day 5 or so.
Human development days 4-7
This new cluster of cells attaches to the endometrial lining of the uterus, where it implants on and begins to
penetrate into the endometrial wall.
During fertilization, the sperm and egg fuse to form a new diploid cell called a zygote.
Meanwhile, the endometrial tissues react to a surge in progesterone released from the corpus luteum,
The zygote's cells divide, forming a new, multicellular cluster called a blastocyst, which travels to the uterus becoming engorged with blood and fluids and swelling up in preparation for the blastocyst’s arrival.
where it implants itself on the inner surface of the uterine wall.
This whole process lasts until around day 7.
A few hours after syngamy, when the sperm and egg have fused into a zygote, the new diploid cell
undergoes a process called cleavage, dividing into a new pair of cells called blastomeres.
The blastomeres keep splitting, becoming a loose clump of four cells, then eight cells, and finally a more
structured, mulberry-shaped 16-cell cluster called a morula, with inner and outer cell masses.
The morula’s cells are held in a vaguely spherical arrangement by the zona pellucida.
The morula gradually develops an outer cell mass of trophoblast cells and an interior cell cluster with a
fluid-filled cavity at the core, which is called the blastocoel.
As soon as the blastocoel forms, the morula is no more: it’s now a water balloon-shaped arrangement of
cells called a blastocyst.
The cells making up the inner cell wall of the blastocyst are collectively called the embryoblast, because
they will go on to form the fetus.
The embryoblast cells cluster together at one end of the blastocyst in an area called the embryonic pole.
Meanwhile, the trophoblast cells flatten out into a barrier around the blastocyst called the epithelial wall.
Fully-formed, the blastocyst hatches from the zona pellucida around the end of day four, and is now ready
to attach itself to the wall of the uterus.
Trophoblast cells help the blastocyst implant into the wall of the uterus by releasing L-selectin molecules
on their surface.
These are proteins which can bind to carbohydrates, and they form a lock-and-key-like attachment to
carbohydrate receptors located on the uterine wall.
Once there, the trophoblast cells begin proliferating and penetrating into the wall—now, these cells are
called syncytiotrophoblast cells.
During implantation, the mucosal tissues of the uterus are in a secretory phase, as a structure called the
corpus luteum begins releasing large quantities of a sex hormone called progesterone into the body.
The corpus luteum is located in the ovary, and it develops in the spot where the unfertilized oocyte (that’s
the egg) was initially released.
Progesterone from the corpus luteum floods throughout the body, reaching the glands and arteries of the
uterus.
In response to the hormone, the uterine arteries become large and coiled, engorging the endometrial layer
(the tissues lining the uterus) with blood.
Summary
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The ventral (underside) layer of the bilaminar disc is called the hypoblast, and it consists of cells that start
to line the fluid-filled cavity containing the embryoblast cells (the blastocoel) which then becomes known
as the yolk sac.
Human development week 2
Oddly enough, this yolk sac contains no yolk.
During the second week of human development, the blastocyst attaches to the wall of the uterus. Instead, it’s filled with fluid, called vitelline fluid, which washes across the embryo, nourishing it during this
early stage.
The cells in the blastocyst's outer layer are called trophoblast cells, and they penetrate into the uterus,
establishing a connection between the blastocyst and the mother. It’s a bit like how small critters in the ocean get nutrients directly from the water!
The cells in the blastocyst’s inner layer are called embryoblast cells, and they turn into a new, flat, two- The dorsal layer of the bilaminar disc is called the epiblast, and it gives rise to all three of the germ layers of
layered structure which eventually gives rise to all of the organs and tissues of the body. the embryo: the endoderm, mesoderm, and ectoderm.
By day 7 or 8, the blastocyst implants on the surface of the endometrial wall, or decidua; the area where it The amniotic cavity develops just above the bilaminar disc, and it gets lined with epiblast cells.
implants is called the decidua basalis.
So we end up with two little balls, right next to each other.
To snuggle deeper into the decidua basalis, trophoblast cells from the outer layer of the blastocyst assemble
into two layers of cells. Meanwhile, in the embryoblast, cells from the hypoblast layer start to differentiate into extraembryonic
mesoderm cells, named this because they are outside of the developing embryo.
One layer is called the cytotrophoblast, which consists of mononucleated cells, and the other is called the
syncytiotrophoblast, which consists of a multinucleated cluster of cells. These are some of the earliest mesoderm cells, and they start to form even while the embryoblast itself is a
bilaminar disc.
Slowly, the syncytiotrophoblast expands into the decidua basalis.
These mesoderm cells line the inside of the cytotrophoblast and syncytiotrophoblast and begin creating
By day 9, the syncytiotrophoblast has pushed deeper into the decidua basalis, and by day 11, the blastocyst space to form what will eventually become the chorionic cavity.
is almost completely buried within it—like a seed getting pushed into soil.
Around day 12, the decidua undergoes the decidual reaction.
High levels of progesterone cause the decidual cells to enlarge, and they become coated in a sugar-rich, Summary
fatty fluid the syncytiotrophoblast can absorb to sustain its growth; this fluid also helps sustain the embryo
early on. Alright, as a quick recap… In week two of human development, the syncytiotrophoblast continues to
expand into the decidua and begins to reorganize into primary villi.
Initially, the decidual reaction only occurs at the decidua basalis, the site of implantation, but eventually it
spreads throughout the entirety of the decidua. Blood vessels from the parent grow nearby and create pools of blood near the villous trees.
Around day 14 of development, syncytiotrophoblast cells start to form little protrusions called primary Inside the blastocyst, the embryoblast differentiates into the epiblast and hypoblast.
villi—each one looks a bit like a tree.
Some cells from the epiblast become the extraembryonic mesodermal cells, which will go on to line the
These primary villi trees form all the way around the fetus, and cells start to clear out from between the chorionic cavity.
primary villi, leaving behind empty spaces called lacunae.
While this is all happening, arteries and veins from the parent start to grow into the decidua basalis.
Normally we think of red blood cells staying confined to blood vessels, but as the placenta develops, an
interesting thing happens: tiny arteries merge with the lacunae, eventually filling these empty spaces with
oxygenated blood.
Veins also merge with lacunae and bring blood back to the parent’s heart.
Over time, more and more of these little pools of blood develop, and they start merging together to form a
single large pool of blood with many arteries delivering blood into it and many veins taking blood away.
This large pool is called the junctional zone, and submerged within it is a little forest of fetal villi trees.
While this happens on the what, for simplicity’s sake, we’ll call the outside of the blastocyst, the inner
embryoblast cells assemble into two layers, forming a flat structure called the bilaminar embryonic disc.
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Around day 15 of development, two areas of the ectoderm layer—one in the cranial region and one in the
caudal region—push ventrally and fuse with the endoderm layer, excluding the mesoderm layer entirely,
forming two new bilaminar regions in an otherwise trilaminar disc.
Human development week 3
The cranial bilaminar region develops into the oropharyngeal membrane which disintegrates in week 4 to
form the opening of the mouth.
During week 3 of human development, the blastocyst is fully embedded in the endometrial tissues, or
decidua, and it undergoes a process called gastrulation, which starts around day 14. The caudal bilaminar region develops into the cloacal membrane, which disintegrates in week 7 to form the
opening of the anus and genitourinary tracts.
During gastrulation, the cells of the blastocyst become reorganized significantly, and by the time the
process is finished, it's no longer a blastocyst at all—it’s a gastrula! Around day 17, a group of mesoderm cells form a solid rod of cells (kind of like the shaft of an arrow)
running through the embryo along the craniocaudal axis. This structure is called the notochord.
Gastrulation begins with the formation of the primitive groove (sometimes called the primitive streak), a
narrow depression that runs down the center of the epiblast layer. The notochord is a transient embryonic structure, meaning that it doesn’t exist as a structure in the adult;
in fact, the only remnant adults have of the notochord is its contribution to the nucleus pulposus, the jelly-
When viewed from above, the groove starts near the tail or caudal end of the embryo, and grows towards like center of the intervertebral discs.
the head, or cranial end.
Nevertheless, the notochord is extremely important during early development for a couple of reasons.
This groove defines the cranial-caudal axis, and the two sides of the groove represent the first instance of
bilateral symmetry in the embryo—a left and right side to the body. First, the notochord is a solid structure, so it helps influence how the embryo folds early on.
Closer to the midline (where the groove is located) is considered medial, and closer to the edges is lateral. Second, the cells of the notochord secrete a protein called Sonic HedgeHog (SHH for short), which diffuses
throughout the trilaminar disc.
If you view the groove from the side, then you can see that the groove forms on the dorsal, or back, side of
the embryo, which makes the dorsal-ventral axis more obvious. The closer a cell is to the notochord, the higher the concentration of SHH, so it’s a way for all of the cells to
know where they are in three-dimensional space. This helps the surrounding tissues differentiate and
The round bilaminar disc also elongates, and starts to resemble a guitar pick, narrow at the caudal end and develop in the right way.
wide at the cranial end.
On day 20, mesoderm cells around the notochord differentiate into three specialized types of mesoderm
At the cranial end of the primitive groove, a small mound of tissue develops called the primitive node, and a called the paraxial mesoderm, intermediate mesoderm, and lateral plate mesoderm, each of which goes on
tiny dimple forms within it, called the primitive pit. to make different tissues and organs.
The primitive groove, primitive node, and primitive pit together form the primitive streak. Try saying that 3 The notochord also starts a process called neurulation where it stimulates surrounding ectoderm cells to
times quickly... thicken and form the neural plate.
Okay, so as the primitive streak forms in the epiblast layer, some epiblast cells start to migrate towards the The neural plate starts to fold and dip down forming a neural groove with edges called neural folds.
primitive groove, move down into the bottom of the groove, and then actually dive right into it. It’s a bit like
a child diving into a ball pit at a funhouse. As the groove continues to grow ventral to the ectoderm layer, the neural folds comes together and they
pinch off from the surface of the ectoderm layer, forming the neural tube.
The epiblast cells that slip through the primitive groove begin to differentiate to form new cell layers.
The neural tube now sits between the mesoderm and the ectoderm.
Some epiblast cells dive deep and form the embryonic endoderm layer; these freshly differentiated
endoderm cells quickly replace the ventral hypoblast cell layer. While the germ layers are becoming apparent, the syncytiotrophoblast cells—the outer cells of the
blastocyst responsible for firmly implanting the embryo within the uterus—are continuing their task of
Other epiblast cells take a more shallow dive and form the embryonic mesoderm layer, which meets up further establishing the connective network between the embryo and the mother.
with the extraembryonic mesoderm layer that was created earlier from the epiblast.
Primary villi along the outer trophoblast layer continue to get more and more submerged within the
The extraembryonic mesoderm also divides into two layers: parietal mesoderm and visceral mesoderm. maternal blood of the junctional zone.
Finally, the epiblast cells that don’t dive into the groove form the embryonic ectoderm layer. In addition, extraembryonic mesoderm cells migrate into the primary villi, forming secondary villi, which
differentiate into small fetal blood vessels that collectively form the villous capillary system, the fetal
So we end up with a three-layered disc called the trilaminar disc with ectoderm, mesoderm, and endoderm
contribution to the placenta.
cell layers.
At this point, the circulatory link between the embryo and the parent is starting to become more firmly
These cell layers are called the germ layers, and they’re multipotent, meaning they can differentiate into
established.
any tissue or organ.
As soon as the fetal heart begins to beat, oxygen and nutrients will begin flowing into the fetus from the
maternal blood through these villi.
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Summary
All right, as a quick recap… In the third week of human development, the primitive streak establishes the
first body axis, and triggers the epiblast layer to differentiate into the three germ layers: ectoderm,
mesoderm, and endoderm.
Soon after, mesodermal cells form the notochord, a structure that releases Sonic hedgehog protein, a
genetic transcription factor that helps to define a three dimensional map for the development of nearby
cells.
The notochord also sparks the process of neurulation in the ectoderm, resulting in the formation of the
neural tube.
Finally, secondary villi develop within the primary villi and help to form the villous capillary system in the
placenta.
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Others will go on to form the epidermis layer of the fetus’ skin, as well as structures associated with the
skin like hair, nail, sweat glands, and mammary glands.
Ectoderm Here’s a story to help you remember the important structures derived from the ectoderm: a man touches
the ectoderm candle on the strawberry cake.
When the embryo is a week old, it has two layers of cells: a dorsal epiblast layer and a ventral hypoblast His skin (epidermis) and nails get burned and turn black (melanocytes), and he feels a sharp pain (in his
layer. central and peripheral nervous system).
During week 3 of development the embryo undergoes gastrulation where the cells in the epiblast layer He pulls his burning finger back, but pokes himself in the face, setting his head on fire.
form a three-layered trilaminar disc with an ectoderm, mesoderm and endoderm layer.
His eyes, ears, nose, hair, and even his teeth get set on fire!
So, imagine the embryo is like a strawberry birthday cake with the ectoderm as the candles, the mesoderm
as the lime frosting, and the delicious sponge cake as the endoderm. In a last ditch effort to put the fire out, his body starts sweating and lactating (sweat and mammary glands)
and even tearing up (pitui-“teary” gland).
We can even put three candles on this cake to help you remember that gastrulation happens during week 3.
During gastrulation, some mesodermal cells start to differentiate and they form a structure called the
notochord, a rod of cells that release different genetic transcription factors that help embryonic cells
Summary
develop into the body's various organs and structures.
The notochord also kickstarts a process called neurulation, stimulating the cells in the nearby ectoderm All right, as a quick recap… The ectoderm is the dorsal most germ layer, and through a process called
layer to thicken and form a layer of cells called the neural plate. neurulation, these cells form the neural tube.
As it forms, the neural plate starts to fold, and it dips down to form a neural groove with edges called neural From the neural tube, neural crest cells migrate to help form the central nervous system, the peripheral
folds. nervous system, the sensory epithelium of the ears, nose, eyes, and mouth, as well as glands such as sweat
glands, mammary glands, and the pituitary gland.
As the groove continues to deepen, ventral to the ectoderm layer, the neural folds comes together and pinch
off from the surface of the ectoderm layer, forming the neural tube.
The neural tube now sits between the mesoderm and the ectoderm.
On the dorsal side of the neural tube where the neural folds fuse, there are special cells called neural crest
cells that migrate out and form a new layer of cells between the ectoderm and neural tube.
Neural crest cells are like little explorers: they migrate throughout the developing fetus to form a variety of
tissues including the peripheral nervous system, melanocytes in the skin, specific parts of the facial bones,
chromaffin cells of the adrenal glands, and parafollicular C cells in the thyroid.
In fact, neural crest cells are responsible for so many of the body’s organs and tissues that you might think
of them as the body’s unofficial fourth germ layer.
At this point, like any hollow tube, the neural tube still has openings at both ends: a large opening at the top
end called the cranial neuropore, and a smaller opening at the bottom end called the caudal neuropore.
The cranial neuropore seals up around day 25, while the caudal neuropore seals up a few days later, around
day 28.
Once the cranial and caudal neuropores have closed, the neural tube is fully formed.
Meanwhile, ectoderm (known as surface ectoderm now that the neural tube has closed) starts to form the
ears and eyes.
Two bumps called the otic placode and the lens placode form near the cranial end of the ectoderm.
Over time, the otic placode will form otic vesicles, which develop into the cochlea and the inner ear.
At the same time, the lens placode develops into the lens and cornea of the eyes.
Finally, many of the ectoderm cells go on to form sensory epitheliums like those in the nose and mouth.
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Meanwhile, the visceral mesoderm goes on to become the serous membrane that covers the various
organs—what we call the visceral pleura—and also gives rise to the muscular wall of the gut and the heart,
as well as the circulatory system.
Mesoderm
To remember this, let’s go back to our old man with the can of frosting.
On day 20 or so, mesoderm cells around the notochord differentiate into three specialized types of Due to the adrenaline and sexual arousal stemming from his birthday disaster, the old man ends up lateral
mesoderm called paraxial mesoderm, intermediate mesoderm, and lateral plate mesoderm, each of which (meaning flat) on the ground because he suffered a massive heart attack (circulatory system).
goes on to make different tissues and organs.
He ends up in a body bag (serous membranes) with an arm and leg sticking out (limb development), and
Paraxial mesoderm forms closest to the notochord and it quickly starts to segment into paired blocks of full of poop because his gut muscles collapse (gut muscles). Worst birthday ever!
tissue called somites, with each somite in the pair flanking the notochord and the neural tube above it.
About three pairs of somites form per day; the number of somite pairs can actually be used to determine
the age of the embryo, sort of like the rings in a tree trunk.
Summary
Somites develop in a cranial-caudal direction; in other words, from head to tail.
All right, as a quick recap… Mesoderm cells first give rise to the notochord, which secretes transcription
By the end of week 5, there are between 42 to 44 pairs of somites in total.
factors that help nearby cells orient themselves in three-dimensional space.
The somites further divide into three regions: sclerotome, which eventually gives rise to the bones and
The nearby mesoderm starts to organize into three types: paraxial mesoderm which turns into pairs of
cartilage; myotome, which gives rise to the muscles; and dermatome, which gives rise to the dermis layer of
somites, which give rise to skin, muscle, and bony tissue; intermediate mesoderm which gives rise to
the skin.
adrenal tissue, gonads, and kidneys; and lateral plate mesoderm, which gives rise to serous membranes,
To help you remember the tissues that derive from paraxial mesoderm and the somites, think back to limb tissue, and the heart and circulatory system.
mnemonic in our last chapter; the one with the frosting on the birthday cake representing the mesoderm
layer.
Imagine an old man trying his hardest to open a can of lime frosting that's closed so-tight (like somite).
He tries so hard that his skin rips (dermis layer), his (muscles) get sore, and his (bones) start aching, but
the lid won’t budge an inch. Poor guy.
The next type of mesoderm is intermediate mesoderm.
This layer’s a bit thinner and located just lateral to the somites.
Intermediate mesoderm gives rise to the adrenal cortex and urogenital structures like the kidneys, and
reproductive organs like the testes and ovaries.
To continue the story, the old man keeps straining to open the frosting can and immediately (like
intermediate) starts jumping up and down on it.
His adrenaline starts pumping (the adrenal glands), he gets a bit sexually aroused (the gonads), and in the
end he strains so hard he ends up peeing his pants (the kidneys). Guy just can’t catch a break.
The final layer is the lateral plate mesoderm, and it’s the thinnest and most lateral of the three types (hence
the name).
Around week 3 of development, the lateral plate mesoderm splits into a dorsal portion called somatic or
parietal mesoderm, which adheres to the ectoderm, and a ventral portion called the splanchnic or visceral
mesoderm, which adheres to the endoderm.
The space between the split is called the intraembryonic coelom or intraembryonic cavity, and this space
eventually becomes the thoracic and abdominal cavity.
The parietal mesoderm goes on to become the serous membrane that covers these two cavities—what we
call the parietal pleura—as well as the soft tissues of the arms and legs.
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The midgut remains connected to the yolk sac; this connection is called the vitelline duct or yolk stalk, and
it gets thinner and thinner as the embryo grows.
Endoderm Endoderm lines the yolk sac, which sits outside of the body of the developing embryo, so the vitelline duct
passes through the umbilical ring to get to the yolk sac.
The endoderm is the innermost germ layer, which makes it easy to remember the body parts it gives rise Over time, the yolk sac gets smaller and smaller, and eventually the vitelline duct collapses; the only
to: stuff inside our bodies, specifically, spaces and cavitations like the gut tube and body cavities that house remnant that’s left behind is Meckel’s diverticulum, a little bulging section in the small intestine that
our internal organs. doesn’t do much of anything.
Endoderm also forms things like the lining of the ear canals, the trachea and respiratory tract, and parts of Like the oropharyngeal membrane, the cloacal membrane breaks down as well, although it happens a little
the bladder and urethra. later—around week 7.
During week 4 of development, the embryo folds in two directions. When that happens, the upper two thirds of the anal canal, which comes from the hindgut, meets up with
the lower one third of the anal canal, which comes from the ectoderm.
In the longitudinal plane, the embryo folds slightly at the cranial and caudal ends, so it looks less like a
pancake and more like a little shrimp. In the adult, the line where they meet up is called the pectinate line.
This is the very beginning of its curling into the fetal position. One way to remember all this stuff formed by endoderm, is to think of our cake analogy.
This folding shapes part of the yolk sac into a gut tube, with the remainder of the yolk sac remaining When you take a bite of that delicious strawberry birthday cake, you open wide so that it doesn’t touch
connected not at the cranial or caudal end, but just in the middle. your mouth; instead, it first touches your pharynx, then your esophagus, before falling all the way through
the gastrointestinal tract.
Now let's switch to the transverse plane, looking at a spot near the middle of our embryo where you can see
the yolk sac. You like this delicious cake so much that you don’t want to poop it out, so it doesn’t get down to the last bit
of the gastrointestinal tract—the part below the pectinate line of the anus.
In the transverse plane, the lateral plate mesoderm splits into a dorsal layer called the parietal (or somatic)
mesoderm layer, and a ventral layer called the visceral (or splanchnic) mesoderm layer. In another scenario, the cake also goes down the wrong way into your trachea, magically forming the lining
of your respiratory tract and lungs.
The parietal layer of mesoderm follows the ectoderm and forms the chest wall and abdominal body wall of
the embryo. So, in addition to becoming the epithelial lining of the gastrointestinal tract and respiratory tract, the
endoderm gives rise to the tonsils, thyroid, parathyroid glands, thymus, part of the liver, gallbladder, and
The visceral layer of mesoderm follows the endoderm and forms the gut tube. pancreas.
More specifically, the endoderm becomes the epithelial cell lining of the gastrointestinal tract while the To remember this, we can build on the analogy. If you want to digest the cake, you need the help of
visceral layer of mesoderm becomes the muscular wall. digestive organs like the pancreas, liver, and gallbladder, so it makes sense that these would be derived
from the endoderm.
The mesoderm also gives rise to serous membranes that become the visceral and parietal pleura.
Moreover, if the cake goes down the respiratory tract, it could get stuck on tissue and organs near the
Two layers of the visceral pleura come together to form the mesentery, a flap of tissue that suspends the
trachea, in places like the tonsils in the throat, the thyroid and parathyroid in the neck, or the thymus in the
gut tube in the abdominal cavity.
chest.
Interestingly, the mesentery was only recently officially classified as a body organ!
Finally, endoderm cells also form parts of the ear, and the epithelial lining of the urethra and urinary
Meanwhile, the ectoderm and parietal layer of mesoderm fold around the dorsal side of the embryo, with bladder.
the two sides meeting up and seamlessly coming together in the midline to form the anterior body wall.
We can remember this last section by thinking of places where you should never stick cake, like in your
Well, we say “seamlessly”, but actually, the yolk sac still pouches out a little. ears, or in the urethra where it might end up in the bladder!
Once that happens, we end up with the hollow gut tube inside the embryo’s body, so in a sense embryonic
folding creates a tube inside a tube.
Summary
The gut tube is divided into three regions: foregut, midgut, and hindgut.
When the oropharyngeal membrane breaks down in week 4, the foregut (including the pharynx) connects All right, as a quick recap… When the embryo folds in the longitudinal plane and in the transverse plane, it
with the mouth, which forms from the ectoderm layer. helps to change the gut tube so that it starts looking like a tube within a tube, with a central vitelline duct
attached to the yolk sac in the middle.
Around week 5, the foregut also gives rise to the trachea and lungs.
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The endoderm ultimately gives rise to the gastrointestinal tract leading from the pharynx to just above the
pectinate line of the anus.
It also gives rise to the liver, pancreas, and gallbladder, the respiratory tract, the tonsils, thyroid,
parathyroid glands, thymus, parts of the ear, and the lining of the urethra and bladder.
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Of course, the body doesn’t have one continuous cavity.
Around day 22, a thick plate of visceral mesoderm called the septum transversum forms just cranial to the
Development of the digestive system and body cavities vitelline duct, and this starts to divide the thoracic cavity and abdominal cavity.
Around the fifth week of development, two flaps of tissue called the pleuropericardial folds grow out of the
During the third week of development, the embryo is a flat, three-layered disc, and each layer contains lateral body wall and fuse together to divide the thoracic cavity into two pleural cavities, which house the
germ cells that give rise to the organs and tissues of the body. lungs, and a pericardial cavity, which houses the heart.
The ventral, or bottom, germ layer is called the endoderm, and it forms the lining of the gut tube and the In the seventh week of development, two more flaps of tissue — this time pleuroperitoneal membrane
respiratory system. tissue — grow ventrally from the body wall and fuse with the septum transversum to completely seal off
the thoracic cavity from the peritoneal cavity.
The middle germ layer is called the mesoderm, and it forms connective tissues like muscles and bones.
At this point, there are pericardial and pleural cavities in the thorax and the peritoneal cavity in the
And the dorsal, or top, germ layer is called the ectoderm, and it gives rise to the sensory organs like the abdomen.
skin, the eyes, and the central nervous system.
There’s also the diaphragm, which is the large muscular organ that separates the abdominal and thoracic
The mesoderm differentiates into the paraxial mesoderm, intermediate mesoderm, and lateral plate cavities.
mesoderm, and, at around day 19, a space forms in the lateral plate mesoderm.
Mesodermal cells from the third, fourth, and fifth pairs of somites penetrate the pleuroperitoneal
This space, called the intraembryonic coelom, or cavity, separates the lateral plate mesoderm into dorsal membranes and form the muscular portion of the diaphragm.
and ventral layers.
Meanwhile, the two crura of the diaphragm, which are the two main tendons that tether it to the vertebral
The dorsal layer is the parietal mesoderm layer, and its cells adhere to cells from the overlying ectoderm column, come from the mesoderm of the lumbar region.
and wrap around the amnion.
The ventral layer is called the visceral mesoderm layer, and its cells adhere to cells from the underlying
endoderm, which covers the yolk sac.
Summary
The parietal mesoderm gives rise to the serous membranes that line the different cavities in the body, and
the visceral mesoderm becomes the serous membrane that covers the lungs, heart, and abdominal organs.
All right, as a quick recap: by the end of week 3, the lateral plate mesoderm divides into parietal and
These membranes are really important because they prevent the organs from getting injured as they rub up visceral mesoderm and they form the serous membranes for the developing organs and also establish the
against each other or against the body wall. pleural, pericardial, and peritoneal cavities.
During the fourth week of development, the embryo undergoes structural changes, transitioning from a Finally, mesoderm from the third, fourth, and fifth somites help give rise to the muscular portion of the
trilaminar disc into a more cylindrical shape. diaphragm.
The combined visceral mesoderm and endoderm layer, which lines the yolk sac, folds rostrally and
caudally, creating a primitive gut tube out of the yolk sac and leaving the remainder of the yolk sac in the
middle section of the gut.
While that's happening, the combined parietal mesoderm and ectoderm folds down with the amnion
forming the lateral body folds, which eventually merge and become the anterior body wall of the embryo,
or what you might think of as the chest.
This creates a gut tube inside a body tube, or, more simply, a tube inside a tube in the rostral and caudal
parts of the embryo.
However, the yolk sac is still poking out in the mid-section.
At this point, the dorsal portion of the yolk sac has become a part of the gut tube, while the connecting stalk
between the yolk sac and gut tube is renamed the vitelline duct.
A ridge of double-layered visceral mesoderm forms the dorsal mesentery, which suspends the gut tube
from the body wall as it dangles in the embryonic cavity.
This pendulous flap of tissue was only recently classified as an organ, and it provides a pathway for blood
vessels, nerves, and lymphatics to reach the various body organs.
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Lots of fetal villi trees next to one another are basically submerged in the pool of maternal blood in the
junctional zone.
Development of the placenta The villi in the junctional zone start to grow more and more branches, whereas the villi that are outside of it
regress.
The placenta is an organ that's co-created by the fetus and the mother during development. Around day 17 of development, fetal mesoderm cells enter the primary villi and they start forming tiny
blood vessels, establishing a basic system of fetal arteries, capillaries, and veins within each villi.
Deoxygenated fetal blood gets to the placenta through two umbilical arteries, and the blood picks up
oxygen and glucose while dropping off carbon dioxide. The villi capillaries connect with blood vessels in the umbilical cord, and this links up the placental and fetal
circulatory networks.
Oxygenated fetal blood then heads back towards the heart through a large umbilical vein.
At this point, the placenta is really starting to take shape.
That umbilical vein and the two umbilical arteries collectively form the vessels of the umbilical cord.
The basal plate, sometimes called the decidual plate, is the thick layer of decidua basalis tissue that the
Development of these structures goes back to the first week of development, when the fetus is just a little maternal arteries (called spiral arteries) and veins have to pass through to get to the junctional zone.
ball of cells called a blastocyst.
This is the maternal contribution to the placenta.
Going forward, we’ll refer to this blastocyst as the fetus just to avoid changing names.
On the other side, we’ve got a forest of villi trees called the chorionic frondosum emerging out of the
By day 7 or 8, the fetus implants on the surface of the endometrial wall or decidua; the point of contact is chorionic plate.
called the decidua basalis.
The chorionic plate is parallel to the basal plate, sandwiching in the junctional zone. This part is the fetal
To snuggle deeper into the decidua basalis, trophoblast cells from the outer layer of the fetus assemble into contribution to the placenta.
two layers of cells called the cytotrophoblast and the syncytiotrophoblast.
Now, while the placenta has been forming on one side, a space forms around the fetus.
The cytotrophoblast is an inner layer of mononucleated cells, and the syncytiotrophoblast is an outer layer
of multinucleated cells with no distinct cell boundaries. This space forms as cells sort of move out of the way, and a new cavity called the chorionic cavity comes
into being.
Syncytiotrophoblast cells don’t undergo cell division which means that their population of cells would be
doomed to simply die out over time without the help of the cytotrophoblast. Within the chorionic cavity is the amniotic cavity, the yolk sac, and the fetus itself.
To replenish the number of syncytiotrophoblast cells, there’s a steady flow of cytotrophoblast cells that The wall of this cavity where the syncytiotrophoblast villi regressed is known as the chorion laeve.
fuse with the syncytiotrophoblast cells, literally merging with them and forming an expanding syncytium.
Stuck to the outside of the chorion laeve is a thin layer of decidua called the decidua capsularis.
It’s a bit like maintaining the population in a retirement community where individuals aren’t raising
youngsters and occasionally pass away, by attracting a steady inflow of new retirees. On an ultrasound, the chorionic cavity shows up as a relatively large, dark space, and it’s used to identify a
pregnancy even before the fetus can be seen.
The multinucleated syncytiotrophoblast grows larger and moves like an octopus deeper into the decidua
basalis. During the fourth and fifth months of development, decidual septa or walls form and divide the placenta
into somewhere between 15 and 20 different regions, called cotyledons.
Around day 14 of development, cells of the syncytiotrophoblast start to form little protrusions called
primary villi—each one looks a bit like a tree. About 100 spiral arteries pump blood into the cotyledons, providing a steady supply of oxygenated blood
for the villi to bathe in.
These primary villi trees form all the way around the fetus, and cells start to clear out from between the
primary villi, leaving behind empty spaces called lacunae. Oxygen, glucose, and other molecules like immunoglobulins, hormones, and even certain toxins are able to
move across the syncytiotrophoblast lining the villi wall, and then move across the endothelial cells lining
While this is all happening, arteries and veins from the mother start to grow into the decidua basalis. the fetal capillaries.
Normally we think of red blood cells as staying confined to blood vessels, but as the placenta develops, an Meanwhile, carbon dioxide makes the opposite journey, leaving the fetal capillaries and entering the
interesting thing happens—tiny arteries start to merge with the lacunae, and these previously empty maternal blood in the junctional zone.
spaces become filled with oxygenated maternal blood.
As the fetus grows, so does the uterus and the placenta—the placenta covers about 15–30% of the uterine
Veins also merge with lacunae and bring that blood back to the maternal heart. wall at any given time during development.
Over time, more and more of these little pools of blood develop and they start merging together to form a The placenta also thickens and by the time the fetus reaches full term, it’s about 20cm across, the size of a
single large pool of blood with many arteries delivering blood into it and many veins taking blood away. frisbee.
This large pool is called the junctional zone—because this is where the maternal and fetal circulations come During the third stage of labor (after the baby is born), the placenta pulls away from the wall of the uterus,
into close contact. since it is no longer needed at that point, and it’s expelled from the body as afterbirth.
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Summary
All right, as a quick recap… The placenta forms a few weeks after the fetus implants in the wall of the
uterus.
On the maternal side, spiral arteries send blood into the junctional zone, and maternal veins take that blood
away.
On the fetal side, chorionic villi (and the tiny capillaries within them) dip into the junctional zone.
The thin endothelial cell wall and the syncytiotrophoblast lining of the villi are all that separate fetal red
blood cells and maternal red blood cells.
Throughout pregnancy, gases and nutrients hop across that barrier to sustain the fetus and help it grow.
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The body stalk, the vitelline duct, and the allantois push together to form the umbilical cord at the site of
the umbilical ring, a fibrous ring of tissue that develops on the abdominal wall of the fetus.
Development of the umbilical cord Between weeks 4–8, the cells lining the amniotic cavity (originally derived from the epiblast cells), start to
generate a lot of amniotic fluid.
During development, the fetus is connected to the placenta via the umbilical cord, a long, flexible stalk that This causes the amnion to swell and take over most of the space in the chorionic cavity.
has two small arteries and a large vein.
As the amnion expands like a big bubble, it folds in and covers the body stalk and vitelline duct, forming an
Deoxygenated fetal blood flows through the umbilical arteries to the placenta where it picks up oxygen and outer membrane for the umbilical cord.
glucose while dropping off carbon dioxide.
Now briefly, around week 6 of development, the fetal intestines grow so quickly that a part of the intestine
Oxygenated blood then heads back towards the fetus's heart through the umbilical vein. squeezes through the umbilical ring into the umbilical cord.
When the baby is born the umbilical cord is no longer needed, so it’s cut off, leaving the navel or belly This is called physiological umbilical herniation, meaning it’s a normal occurrence, and by the end of the
button. third month of development the intestines withdraw completely back into the abdominal cavity.
In week 2 of development, the blastocyst has two parts—an inner part called the embryoblast, and an outer So, looking at the umbilical cord in cross-section—there’s the outer layer of amnion, and then there’s the
part called the trophoblast, which develops into the cytotrophoblast and syncytiotrophoblast. vitelline duct, which has its own arteries and veins and is connected to the yolk sac.
The embryoblast has two layers called the epiblast, which contains the amniotic fluid, and the hypoblast, There’s also the allantois, and finally the two umbilical arteries and a single umbilical vein.
which contains the yolk sac filled with vitelline fluid that can nourish the embryo.
After the formation of the umbilical cord, the vitelline duct and yolk sac starts to shrink and eventually
Cells from the epiblast layer start to differentiate into extraembryonic mesoderm cells, so-named because disappear.
they are outside of the developing embryo.
In rare cases, the vitelline duct won’t regress all the way, and will leave behind a tiny remnant in the
These are some of the earliest mesoderm cells, and they start to form even while the embryoblast itself is a midgut—an outpouching of the intestines that’s called a Meckel’s diverticulum.
bilaminar disc.
The allantois goes on to form the fetal urachus, a duct connecting the bladder to the yolk sac, and ultimately
These mesoderm cells line the inside of the cytotrophoblast and syncytiotrophoblast and form the chorion. becomes the median umbilical ligament—the fibrous cord left behind when the urachus closes.
As development progresses, a space called the chorionic cavity develops between the embryoblast and the By the time of birth, all that remains within the umbilical cord is the umbilical vein, the two umbilical
chorion, and these two structures are connected by a short band of extraembryonic mesoderm called the arteries, and a gelatinous substance called Wharton's jelly that protects the umbilical vessels.
body stalk.
After birth the umbilical vein becomes the liver’s round ligament, and the umbilical arteries become the
The body stalk contains the umbilical vessels and is the first of three structures that make up the umbilical medial umbilical ligaments.
cord.
To keep it straight—think of the fact that there are two umbilical arteries, so all the umbilical arteries
In week 3 of development, the embryo folds in two directions. become medi-all ligaments, whereas there’s only an allantois, which turns into the medi-an ligament.
In the longitudinal plane, there is a cranial and caudal fold, so that the embryo now looks less like a pancake
and more like a little shrimp.
The folding process shapes part of the yolk sac into a gut tube, with the rest of the yolk sac remaining Summary
connected not at the cranial or caudal end, but just in the middle of the fetus.
All right, as a quick recap… The umbilical cord is made up of three key structures—the body stalk, the
The endoderm layer, which derives from the epiblast, forms the gut tube and soon divides into three
vitelline duct, and the allantois.
parts—the foregut, the midgut, and the hindgut.
There is also a normal process called physiological umbilical herniation where the intestines briefly
The midgut is open to the yolk sac via a connection called the vitelline duct, which is the second structure in
protrude into the umbilical cord as well.
the umbilical cord.
The vitelline duct regresses completely but in some cases will leave behind a Meckel’s diverticulum.
Around the same time, the hindgut grows a little outpocketing called an allantois, which grows towards the
umbilical cord and drains the bladder. The allantois becomes the urachus, which ultimately regresses into the median umbilical ligament.
The allantois is the third structure in the umbilical cord. Following birth, the umbilical vein becomes the round ligament of the liver, while the two umbilical arteries
become the medial ligaments.
In week 4 of development, the amniotic cavity folds down and around the embryo.
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The chorion develops chorionic villi, tree-like projections that invade into the endometrium of the uterus
and eventually help form the fetal part of the placenta.
Development of the fetal membranes During week 3, the embryo changes its shape—it folds along its two axes and goes from looking like a flat
disc to a curved tube, so that the embryo looks a bit like a shrimp.
The fetal membranes, sometimes called extraembryonic membranes, are tissues that form in the uterus The folding also pinches the yolk sac so that it resembles a balloon that’s squeezed through a ring.
during the first few weeks of development and develop along with the growing embryo.
The part of the yolk sac that goes within the embryo is called the gut tube and it becomes the digestive
These are the amnion, the yolk sac, the chorion, and the allantois, and each of these membranes starts out tract; the narrow, pinched portion is the vitelline duct; and the remainder keeps the name the yolk sac.
as a thin sheet of tissue that surrounds a fluid filled cavity.
Finally, the last of the fetal membranes, the allantois, develops as a tiny outpouching from the rear part of
The first membranes to form are the amnion and the yolk sac. the gut tube called the hindgut.
At the beginning of week 2, the embryo is not quite an embryo yet—it's just a blastocyst, and the blastocyst The allantois is a thin tube that grows up towards the umbilicus, and behind it develops the bladder.
is partially embedded into the endometrium of the mother.
The allantois becomes a canal through which urine can exit the bladder before the urethra develops.
The blastocyst has two parts: an outer cell mass called the trophoblast and an inner cell mass called the
embryoblast. Between weeks 4-8, the amnion starts secreting a lot of amniotic fluid and this causes the amniotic cavity to
swell and fold down and around the embryo, becoming a fluid-filled sac protecting and insulating the
The trophoblast is divided into the cytotrophoblast, which forms the wall of the blastocyst, and the embryo.
syncytiotrophoblast, which is outside the wall and invades into the uterus.
Eventually the amnion and the chorion fuse together and form the amniotic sac.
The embryoblast is a bilaminar disc with a dorsal epiblast layer and a ventral hypoblast layer.
Meanwhile during week 4, the allantois, the vitelline duct, and the body stalk combine to form the umbilical
During day 8, a tiny space called the amniotic cavity forms between the epiblast and cytotrophoblast. cord.
The epiblast cells migrate to form a thin membrane called the amnion that surrounds the amniotic cavity, Over time, the nutritious yolk sac contents get used up, and the yolk sac and vitelline duct shrink and
separating it from the cytotrophoblast. eventually disappear.
During day 9, hypoblast cells begin to migrate to form a thin membrane lining the rest of the blastocoel, The allantois degenerates into a fibrous structure called the urachus, that remains attached to the urinary
forming the walls of the yolk sac. bladder.
The yolk sac fills with fluid, called vitelline fluid, which washes across the embryo, nourishing it during this
early stage.
So basically, by the middle of the second week, the two-layered embryonic disc is sandwiched between the Summary
amniotic cavity and the yolk sac.
All right, as a quick recap… The four fetal membranes that develop in order to support and nourish the
By day 10, some epiblast cells differentiate into extraembryonic mesoderm, and they settle between the
developing fetus include the amnion, the yolk sac, the chorion, and the allantois.
amniotic cavity and the cytotrophoblast, eventually creating a thick layer of extraembryonic mesoderm
tissue between the two. The chorion and amnion form the amniotic sac, which is filled with amniotic fluid in which the fetus is
suspended by the umbilical cord.
Then, over time, a space starts to form within this thick layer of extraembryonic mesoderm.
The chorion also forms the fetal part of the placenta, helping in the exchange of nutrients, waste products
The cells migrate either towards the amniotic cavity and yolk sac side or towards the cytotrophoblast side,
and gases between the fetus and the mother.
leaving behind a space in the middle.
The allantois, along with the vitelline duct of the yolk sac are incorporated into the umbilical cord but
This space is called the extraembryonic coelom or chorionic cavity, and it continues to expand, until there’s
degenerate early in pregnancy.
eventually just a thin layer of extraembryonic mesoderm cells lining the amniotic cavity and the yolk sac
and another thin layer lining the cytotrophoblast.
The one spot where the cavity doesn’t form is at the body stalk, which is where the embryoblast still
remains attached to the wall.
At this point, the wall is composed of a layer of extraembryonic mesoderm, then cytotrophoblast, and
finally syncytiotrophoblast, and together this is called the chorion.
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During a single-child pregnancy, one embryo grows inside a fluid-filled bubble called the amniotic sac, and
receives nutrients and gases from the parent via the umbilical cord and placenta.
Development of twins With twins, two embryos arise, but this doesn’t necessarily mean each fetus gets its own individual ticket to
the placenta buffet and a separate amniotic sac to hang out in.
In most pregnancies a single embryo develops in the uterus, but in some cases, two embryos develop Twins’ access to maternal real estate depends on when exactly the split occurs to turn one embryo into two.
together. These are called twins.
Early in development, there’s a single ball of cells called a blastocyst.
Most twins are fraternal or dizygotic twins, meaning that they originate from two separate eggs that are
fertilized individually. This develops an inner layer called the embryoblast, and an outer layer called the trophoblast.
A minority are identical or monozygotic twins, meaning that they originate from a single zygote that Seven or eight days following fertilization, the trophoblast cells on the outside differentiate into two cell
quickly splits into two separate groups of cells. layers: the cytotrophoblast and the syncytiotrophoblast.
Fraternal twins are from two separate eggs that are fertilized by different sperm, so they have completely Because these cell layers are responsible for establishing the fetal part of the placenta, the moment the
separate genetic makeups. embryoblast divides into two affects how the cytotrophoblast and syncytiotrophoblast develop to
accommodate the pair of embryos.
They don't look any more or less alike than regular siblings, although the resemblance can still be very
close—you may be surprised to learn that Mary-Kate and Ashley Olsen, for example, are fraternal twins, not If the split occurs within two or three days following fertilization, the twins are known as dichorionic-
identical twins. diamniotic—they develop completely separately from one another, receiving nutrients from separate
placentas and swimming about in their own amniotic sacs.
Fraternal twinning occurs at a rate of about 10 per 1000 births worldwide.
If the embryo divides between three and eight days following fertilization, the twins are monochorionic-
Most of the time, fraternal twinning happens when the ovaries release two eggs simultaneously, which is diamniotic; in this case, the trophoblast has already differentiated, so they’ll share a single placenta, but the
called hyperovulation, instead of releasing one egg at a time. umbilical cords will feed into two different amniotic sacs.
Research suggests that some mothers of fraternal twins may produce an overabundance of a hormone If the embryo splits between eight and thirteen days after fertilization, the twins are monochorionic-
called follicle-stimulating hormone, or FSH, which stimulates the growth of ovarian follicles. monoamniotic; twins of this type share an especially close bond, growing together in the same amniotic sac
and receiving nutrients from the same placenta.
People who become pregnant with fraternal twins tend to be taller and heavier on average, with shorter,
more frequent menstrual cycles, all of which are characteristic of having high levels of follicle-stimulating
hormone.
Because follicle-stimulating hormone levels gradually rise with age, fraternal twin pregnancies become Summary
increasingly likely in people aged 35 or older, and this also helps explain why parents who have given birth
to fraternal twins once are more likely to do so again. All right, as a quick recap… Fraternal twins are the product of two separate eggs being released at the same
time during ovulation, which are fertilized by two different sperm.
The likelihood of having fraternal twins resulting from hyperovulation is thought to have a genetic
component, but no specific gene has been identified yet. Identical twins start out as a single zygote that split into two separate embryos at some point during the
first thirteen days of development.
Identical twins are less common than fraternal twins, occurring at a rate of about 4 per 1000 births
worldwide. There can be mono-mono twins that share a placenta and amniotic sac, mono-di twins that share a placenta
but develop in separate amniotic sacs, or di-di twins which develop their own placentas and amniotic sacs.
Identical twins come from a single zygote splitting to form two separate embryos with identical genetic
material.
The split can happen at any time during the first thirteen days of development, and how and when this
division occurs affects how the identical twins share space and resources in the uterus.
Because identical twins have identical DNA, they share many physical traits that have a strong genetic
basis, like biological sex, hair and eye color, blood type, and other physical features.
In fact, subtle differences between identical twin babies actually shows how the environment—even the
environment of the uterus—can affect development!
Identical twins can be categorized based on how they share space and resources in the womb.
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The embryonic cells nearest to the notochord get exposed to a high dose of Sonic Hedgehog protein, while
the embryonic cells furthest away are exposed to a lower dose of Sonic Hedgehog protein.
Hedgehog signaling pathway In other words, there’s a concentration gradient.
It’s similar to what happens when a drop of red dye falls in a bucket of water: the areas closest to where the
The hedgehog signalling pathway is a pathway based on three specific proteins called the hedgehog dye is dropped will be red, and the red color fades the further the dye diffuses into the water.
proteins.
So, the amount of Sonic Hedgehog protein that binds to an embryonic cell tells that cell where it is in three
The most well-studied of these proteins is the Sonic hedgehog protein, or SHH, which plays a key role in dimensional space relative to the notochord, which is the source of the Sonic Hedgehog protein.
structuring the general shape of the body, called patterning.
So, in our example, this cell marked number 2 might know to differentiate into brain tissue, whereas this
During the third week of development, a solid rod of mesoderm called the notochord forms at the midline one, marked 3, knows it should differentiate into an arm.
of the embryo.
Now, if the notochord keeps producing Sonic Hedgehog protein, it might seem like over time the entire
The notochord is extremely important during early development because it helps influence how the chessboard would be completely saturated with the protein, with each square receiving the same amount.
embryo folds.
The reason this doesn’t happen is because the proteins naturally degrade over time.
It also guides how the various tissues differentiate and develop so that the embryo ends up with two arms,
two legs, and one head, instead of some other combination. Okay, so now we’ve established that cells can identify where they are in relation to the notochord.
Groups of proteins in the notochord secrete proteins that guide this process. However, a cell on one side of our chessboard would still have no way of distinguishing itself from a cell in
the same location on the opposite side, since they both got the same amount of Sonic Hedgehog protein.
These include Desert hedgehog protein (DHH), Indian hedgehog protein (IHH), and Sonic Hedgehog protein
(SHH). And many of the cells that are really far away might not get any proteins at all!
Desert and Indian Hedgehog protein were named first, and Sonic was named a bit later—if you played That’s why it’s helpful that the notochord secretes several different Hedgehog proteins—not just Sonic
video games in the ‘90s, you'll know that it’s named after the fast-moving rodent, Sonic the Hedgehog! Hedgehog protein.
The Hedgehog proteins are ligands, meaning they’re molecules that move from one cell over to another and Here, we’ve got Desert Hedgehog protein (DHH), represented in green, which creates a gradient coming
facilitate communication—like letters that one cell might send to another cell around the corner. from the bottom of the notochord.
Early in development, the notochord sends all three Hedgehog proteins out to undifferentiated cells Then there’s Indian Hedgehog protein (IHH), represented in red, creating a gradient coming from the
throughout the entire embryo. middle of the notochord.
When Sonic Hedgehog protein gets released, it slowly diffuses through the interstitial liquid and binds to a Now each square of the board has been exposed to varying levels of the three different proteins, with each
receptor called patched (ptc), which can be found on the cell membranes of embryonic cells. square getting a relatively unique combination.
The patched receptor inhibits the embryonic cell from differentiating, but Sonic Hedgehog protein inhibits In fact, in our example, if you were told that a cell with two blue and two red proteins (and no green
patched, meaning it inhibits the inhibitor! proteins) will give rise to the arm, then you should be able identify which cells those would be—this one on
the left, and this one on the right.
Without the inhibition usually imposed by patched, the embryonic cell starts to activate specific genes that
allow it to differentiate. In fact, that’s why the two sides of the body are largely symmetrical.
But every embryonic cell doesn’t differentiate in the same way—some might activate genes that allow them
to be part of a leg, whereas others might activate genes that allow them to be part of an ear.
Summary
The precise set of genes that get expressed in one cell versus another cell depends on how much Sonic
Hedgehog protein reaches the embryonic cell, and how long the embryonic cell is exposed to Sonic
Hedgehog protein. All right, as a quick recap, the notochord makes various proteins, including Sonic Hedgehog protein, which
binds to the patched receptor on embryonic cells.
One way to think about this is that it’s the cumulative dose of Sonic Hedgehog protein that determines
which genes get expressed and, ultimately, what each embryonic cell turns into. Sonic Hedgehog protein diffuses through the embryo, creating a concentration gradient.
When Sonic Hedgehog protein is released by the notochord, it diffuses throughout the embryo, forming a This, along with other proteins released by the notochord, helps each embryonic cell identify exactly where
concentration gradient. it is in three-dimensional space and develop accordingly.
To better visualize this, let’s look at a grid, and say each square in the grid is an embryonic cell.
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Some of the myocardial cells in the sinus venosus begin to produce a rhythmic electrical discharge at this early
stage.
Development of the cardiovascular system However, the conduction system and working myocardium are still underdeveloped, and they can’t contract in
perfect sync, so we don’t hear the familiar “lub-dub” of the heart at this point.
The cardiovascular system starts developing at the beginning of week 3 of intrauterine life. During craniocaudal folding, the now-cylindrical embryo curves down its length, forming more of a shrimp-like
creature, and this process pushes the heart tube down towards the chest.
At that point, the embryo is a flat little pancake made up of two layers: the epiblast on the dorsal, or back, side,
and the hypoblast on the ventral, or front, side. By the beginning of week 4, the heart tube reaches the thorax, and blood can be seen going through the heart
tube.
A line called the primitive streak appears on the epiblast back of this two-layered creature.
The heart tube develops sections. First there’s the sinus venosus, which has a left and a right sinus horn that
Cells migrate along the primitive streak during gastrulation, resulting in a three-layered embryo pancake, with
bring blood in.
each layer containing germ cells that form organs and tissues of the body.
Above it, there’s the primitive atrium and then the primitive ventricle, which are separated from one another by
The ventral, or bottom, germ layer is called endoderm, the dorsal, or top, germ layer is called ectoderm, and the
the atrioventricular sulcus.
layer in between these two is called mesoderm.
The primitive atrium gives rise to the left and right atria, and the primitive ventricle forms the left ventricle.
The heart derives from a part of the mesoderm called the visceral mesoderm.
The primitive ventricle is separated from the next region, called the bulbus cordis, by the bulboventricular
Let's look at this three-week-old creature from above. Mesoderm cells go through the primitive streak and make
sulcus.
their way up to the embryo’s head, forming an area that’s called the primary heart field, a horseshoe-shaped
area that has two limbs, with one on either side of the future brain. The first part of the bulbus cordis forms the right ventricle, as well as the outflow tracts for both ventricles.
This region lies on a blanket of endoderm cells that secrete vascular endothelial growth factor, which is called Finally, at the top of the heart tube, there’s the truncus arteriosus, which pumps blood through the aortic sac
VEGF for short. into an early version of the circulatory system that’s made up of aortic arches.
VEGF signals the cells in the limbs of the horseshoe to self-organize into two heart tubes. This organization of structures doesn’t mirror the adult heart, so during week 4 the heart tube undergoes
looping, which is a fancy way of saying the tube elongates, its walls become thicker, and sections of the heart
A primitive pericardial cavity also appears lateral to each endocardial tube.
move around so that they end up in their right place.
At its inferior end, each endocardial tube connects to a vitelline vein, which comes from an extraembryonic
The heart tube is held in place inside the pericardial cavity by blood vessels at both ends, and looping starts with
tissue called the yolk sac and through which blood enters the endocardial tube.
the heart tube folding into a “C” shape.
Blood exits each endocardial tube at its superior end through a dorsal aorta, which then continues down the
The truncus arteriosus and bulbus cordis move down and to the right to form the top portion of the “C”, while
embryo’s back.
the primitive ventricle bends to the right of the midline and a little to the front, forming the middle of the “C”.
During lateral folding, the flat embryo goes from a trilaminar disc to a more cylindrical shape.
Finally, the primitive atrium and sinus venosus form the bottom of the “C” and snuggle deeper inside the
The lateral borders of the embryo reach out towards each other and meet anteriorly at the midline, forming a pericardial cavity.
cylindrical shape.
As development continues, the growing ventricle moves to the left, so it crosses over the midline again, covering
This process makes the two endocardial tubes fuse into one, forming the primitive heart tube. the primitive atrium.
The left and right vitelline veins also fuse to form the sinus venosus, which is the inflow tract of the heart tube. By the end of week 4, the cardiac loop starts to take on the general appearance of the adult heart.
Similarly, the aortae fuse to form the aortic sac, which is the outflow tract of the heart tube. Also, by this point, visceral pericardium has attached to the outside of the heart, forming the epicardium.
The two pericardial cavities also unite around the heart tube and form the singular pericardial cavity. However, on the inside, the definitive cardiac chambers have yet to partition.
The heart tube remains attached to the back wall of the pericardial cavity by a sheet of mesoderm called the By looking at the heart from another angle, we can see that the primitive atria and the primitive ventricle initially
dorsal mesocardium. communicate through the atrioventricular canal.
The heart tube itself has two layers: an endothelial lining on the inside, which turns into the endocardium, and On the anterior and posterior walls of the atrioventricular canal, the mesoderm proliferates and forms anterior
cardiac myoblasts on the outside, which become the myocardium. and posterior endocardial cushions.
These cushions grow towards each other and fuse, separating the heart into the left and right atrioventricular
canals.
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On the ventricular side of both the right and left atrioventricular canals, endocardial cells proliferate to form the Over time, the sinus venosus becomes asymmetric.
leaflets of the mitral and tricuspid valve, as well as the rest of the valvular apparatus. This divides the atria from
the ventricles. It shifts to the right, with the right sinus horn becoming the smooth-walled part of the right atrium, as well as
the openings for the superior and the inferior vena cavas.
Inside the atrium, a tissue called the septum primum grows downward between the left and right atria, slowly
creating two separate chambers and closing a gap called ostium primum, which means the “first opening.” Meanwhile, the left sinus horn shrinks and persists only as the coronary sinus and the oblique vein of the left
atrium.
This septum primum then fuses with the endocardial cushion and closes the gap completely.
In the wall of the sinus venosus, a special group of myocardial cells organize and synchronize their electrical
Meanwhile, a hole appears in the upper area, called the ostium secundum, or “second opening.” discharges, forming the sinoatrial node and taking over as cardiac pacemaker near the entrance of the superior
vena cava.
Now, we also have the septum secundum which grows downward just to the right of the septum primum, and
covers the ostium secundum like a curtain. Soon after the sinoatrial node has developed, another group of cells located in the atrioventricular septum
organizes in the atrioventricular node, which is the secondary pacemaker center.
This leaves a small opening called the foramen ovale, and essentially creates a makeshift valve that allows blood
to go from the right atrium to the left atrium during fetal life. At the same time, cells in the interventricular septum differentiate into specialized conducting cells that form
the bundle of His.
The ventricles separate when a muscular ridge of tissue grows upward from the apex, or the tip, and then fuses
with a thinner membranous region coming down from the endocardial cushions. Voila: two separate ventricular Cells in the rest of the ventricular myocardium differentiate into the conducting cells that form the Purkinje
chambers. fibers.
Now, if we jump back to the outside of the heart, we see that each of these new chambers is still connected
through their outflow tracts to the truncus arteriosus, meaning that blood just mixes from the two chambers. Summary
The truncus arteriosus begins to divide into the aorta and the pulmonary artery when two endocardial cushions
All right, as a quick recap: the cardiovascular system starts developing from the primary heart field region of the
appear on the right-superior and left-inferior walls.
mesoderm during week 3 of prenatal life.
These grow with a spiraling trajectory — imagine a corkscrew — and they wrap around each other, forming the
It begins as a horseshoe-shaped structure with a pair of tubes that fold and loop around to put the primitive
aorticopulmonary septum.
heart structures in the right position.
This divides the truncus into the roots of the of the aorta and the pulmonary artery, so now blood gets routed to
Afterwards, cardiac septa develop and partition the heart, producing to two ventricles and two atria.
the right place.
The conduction system of the heart is initially in the sinus venosus, but when the sinus is absorbed by the right
Semilunar valves develop shortly thereafter.
atrium, pacemaker cells become the sinoatrial node in the right atrium wall.
The rest of the aorta and the pulmonary artery come from the aortic arches.
The aortic arches only exist briefly between weeks 4 through 6, and they sprout one after another from the
aortic sac.
Initially, there are 6 aortic arches on each side of the sack, but the fifth arch degenerates and doesn’t turn into
an adult structure.
This means that the remaining arches are numbered 1, 2, 3, 4, and 6.
The first and the second arches disappear very quickly, but they leave behind the maxillary and the stapedial
arteries, respectively, which branch off the internal carotid arteries.
The third arch becomes the two common carotid arteries and part of the internal carotid arteries.
The left fourth arch forms the aortic arch, and the right fourth arch forms the right subclavian artery.
The sixth arch forms the pulmonary arteries, and, on the left side, it also forms the ductus arteriosus, which is a
fetal structure through which blood from the pulmonary artery shunts directly into the aorta, bypassing the
immature lungs.
Now, we can’t forget about the other, venous side of the heart and the sinus venosus, which initially opens in
the center of the primitive atrium.
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This leads to increased resistance to blood flow in the arterioles, and so the pulmonary artery has really high
pressure.
Fetal circulation This high pressure causes the right ventricle and the right atrium to remain at relatively high pressures as well.
Therefore, the overall pressure on the right side of the heart is much higher than the pressure on the left side of
In healthy adults, oxygenated blood is sent from the left atrium to the left ventricle and then out through the the heart.
aorta to the arteries in the rest of the body.
Now, in the fetal heart, there’s an opening between the atria called the foramen ovale, which is the third
Blood then returns through veins to the right atrium and goes into the right ventricle, which pumps this blood to adaptation of fetal circulation.
the lungs in order to drop off carbon dioxide and pick up oxygen.
The foramen ovale is an opening made by a tiny flap of heart tissue that acts like a one-way valve.
In the fetus, the lungs are not mature enough to complete this last step, so oxygenation happens in the placenta.
That opening shunts, or moves blood, from the higher pressure right atrium to the relatively lower pressure left
Four key adaptations, or structures, make this possible. These are the umbilical veins and arteries in the atrium.
umbilical cord, the ductus venosus, the foramen ovale, and the ductus arteriosus.
So, most of the blood actually bypasses the right ventricle and lungs completely and goes straight to the left
So, imagine that you're an oxygen rich red blood cell that has to get from the placenta to the fetal tissues. atrium and left ventricle before it’s pumped through the aorta to the rest of the body.
Blood from the placenta is highly oxygenated, and from the placenta, this blood heads through the umbilical Only some of the blood from the right atrium goes down into the right ventricle, and this blood enters the
vein, the first adaptation of fetal circulation, toward the liver. pulmonary artery and heads to the lungs.
When the umbilical vein reaches the liver, it branches into the left and right umbilical veins. For the red blood cells in the high-pressured pulmonary artery, there’s a small blood vessel connecting the
pulmonary artery and the aorta called the ductus arteriosus, which is the fourth adaptation of fetal circulation.
The left umbilical vein dumps blood into the portal vein, which goes into the liver.
The ductus arteriosus then shunts blood from the higher pressure pulmonary artery to the relatively lower
The blood in the portal vein goes out to every lobule of the liver, and it becomes deoxygenated.
pressure aorta.
This deoxygenated blood enters the hepatic vein, which then drains into the inferior vena cava, which is one of
This opening is kept open in part by a chemical called prostaglandin, which is made by the placenta during fetal
two enormous veins that carry deoxygenated blood from the lower half of the body to the right atrium.
development.
Now, from the left umbilical vein, a vessel called the ductus venosus forms and connects to the inferior vena
The aorta then sends blood to the entire body through its various branches.
cava.
Now as the aorta goes down it splits into the right and left common iliac arteries, and those both split into
This bypasses the liver circulation, and it represents the second adaptation of fetal circulation.
internal and external iliac arteries.
From the inferior vena cava, the oxygenated blood from the placenta mixes with the deoxygenated blood from
Each of these internal iliac arteries give rise to an umbilical artery.
the lower body.
These two umbilical arteries travel alongside the umbilical vein and bring deoxygenated blood back to the
This mixture of blood is joined by the blood from the hepatic vein before it all flows into the right atrium.
placenta, where it drops off carbon dioxide and picks up oxygen. The cycle repeats itself this way until birth.
Meanwhile, deoxygenated blood from the upper body flows through the other enormous vein, the superior
Now at birth, everything changes. As soon the baby is born, the baby begins to cry.
vena cava, into the right atrium.
Air flows into the lungs for the first time, and it replaces the water that previously filled the alveoli.
Ultimately, the oxygenated blood from the placenta and the deoxygenated blood from the entire fetal body mix
together in the right atrium. As oxygen levels in the lungs and the blood rise, the hypoxic vasoconstriction goes away, and the smooth
muscles around the pulmonary arterioles relax.
Before birth, the fetus’ lungs don’t play a role in gas exchange because there’s no breathing in the womb.
The pulmonary resistance falls, and so does the pressure in the pulmonary artery.
As a result, the arterioles, or tiny arteries, of the lungs are constantly in a low-oxygen environment.
Blood can easily flow into the lungs, which means that suddenly the pressure on the right side of the heart is
As a result of this, a process called hypoxic pulmonary vasoconstriction happens. More specifically,
much lower than pressure on the left side of the heart.
vasoconstriction, or narrowing, of the pulmonary arteries due to the hypoxic, or low oxygen, conditions takes
place. This pushes the flap of tissue that forms the foramen ovale in the opposite direction, and, like a one-way valve, it
doesn’t allow blood to go from the left atrium to the right atrium. Instead, this process basically shuts off the
In other words, the smooth muscle around all of the arterioles in the lung squeezes down when it senses low
foramen ovale.
oxygen levels.
Over time, the tissue seals shut permanently, forming the fossa ovalis.
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All the blood in the right atrium now goes directly into the right ventricle, where it gets pumped into the
pulmonary artery and the lungs.
This drop in pulmonary artery pressure also means that there is a temporary reversal in blood flow through the
ductus arteriosus.
Blood from the aorta now shunts into the pulmonary artery.
This is only temporary, though, because the higher oxygen levels in the blood cause the smooth muscles in the
walls of the ductus arteriosus to constrict.
After delivery, the placenta is separated from the baby, meaning that prostaglandin levels fall.
This also contributes to the closing of the ductus arteriosus.
A few hours after birth, the ductus arteriosus begins closing up and the vessel flattens out and eventually seals
completely, forming the ligamentum arteriosum.
Another postnatal change happens to the two umbilical arteries and the umbilical vein, which are surrounded by
a yellow, gooey substance called Wharton’s jelly in the umbilical cord.
When exposed to the cold world outside the womb, Wharton’s jelly shrinks down and squeezes the umbilical
blood vessels, causing them to wither.
The smooth muscle in the walls of the umbilical arteries constricts and then flattens out like strands of pasta.
Within a few months, the umbilical arteries are mostly gone, and only a central portion remains.
This functions as the superior vesical arteries, which supply blood to either side of the bladder.
Meanwhile, the blood in the umbilical vein and the ductus venosus clots over a period of days, and the blood
flow eventually stops.
The remnants of the umbilical vein form the round ligament of the liver, and the remnants of the ductus venosus
form the ligamentum venosum of the liver.
Summary
All right, as a quick recap… During development, the fetal circulatory system contains four key adaptations: the
foramen ovale, the ductus arteriosus, the umbilical arteries and vein, and the ductus venosus.
Once the baby is born and takes a breath, lots of changes take place. The foramen ovale becomes the fossa
ovalis, the ductus arteriosus becomes the ligamentum arteriosum, the umbilical arteries become the superior
vesical arteries, the umbilical vein becomes the round ligament of the liver, and the ductus venosus becomes the
ligamentum venosum.
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The first stage is the pseudoglandular stage, and it lasts from week 5 to week 16.
During this time, the bronchial buds divide into a left and right main bronchus, and these divide again into three
Development of the respiratory system secondary bronchi for the three right lung lobes and two secondary bronchi for the two left lung lobes.
Secondary bronchi turn into ten tertiary bronchi on the right side and eight on the left—corresponding to the
The respiratory system starts developing during week 4 of intrauterine life, and it begins when a lung bud number of lung segments on either side.
sprouts out of the primitive digestive tract.
Tertiary bronchi divide repeatedly until all the terminal bronchioles are formed.
The lung bud is an outgrowth of the foregut portion of the digestive tract, and it turns into lower respiratory
tract structures such as the larynx, trachea, and lungs. So, now the lungs enter the second stage of development, called the canalicular stage.
Around week 4, the embryo has developed all three embryonic germ layers, and of the three, respiratory tract This stage lasts from week 16 to week 26, and during this time the terminal bronchioles continue to divide and
structures arise from the endoderm and mesoderm. form the respiratory bronchioles.
The larynx starts developing at the beginning of week 4, as nothing more than a slit between the fourth and the Each respiratory bronchiole then divides into three to six alveolar ducts.
sixth pharyngeal arches.
A great number of pulmonary capillaries also form during this stage, making the lungs highly vascular organs.
The pharyngeal arches are paired, symmetrical embryonic structures that sprout from the foregut and arch
towards the embryo's front midline. Starting with week 24, the first primitive alveoli appear in the lung regions closest to the trachea.
They consist of a mesoderm core and that mesoderm is made up mostly of mesenchyme—a soupy, fetal tissue However, these alveoli are immature, in that they have a lining of cuboidal epithelial cells that is not perfectly
that eventually turns into circulatory tissue, lymphatic tissue, and musculoskeletal tissue. adapted to gas exchange just yet, and there’s still very few of them!
The arches are covered on the outside by the pharyngeal cleft, which is made of ectoderm, and lined on the Next is the third stage of development, called the terminal sac stage.
inside with the pharyngeal pouch, which is made of endoderm.
It lasts from week 26 to birth, and during this time more primitive alveoli, sometimes called terminal sacs, form
In fish, these arches develop into gills, but in our case they serve as a foundation for many important structures around each alveolar duct.
around the head and neck.
In addition, the cells of the epithelial lining differentiate into type I and type II pneumocytes, and more
The endoderm of the 4th and 6th pharyngeal arches forms the laryngeal epithelium and glands, and the capillaries form around the primitive alveoli.
mesoderm forms the laryngeal cartilages, while the arches themselves carry the laryngeal branches of the vagus
Type I pneumocytes are flat cells that are in direct contact with the capillaries.
nerve to these structures.
The blood-air barrier forms at the point where the endothelium of the capillaries meets the endothelium of the
All in all, these two arches give us our ability to talk. Doesn’t beat breathing under water, but still pretty cool,
type I pneumocytes (including the basement membrane between).
right?
Type II pneumocytes are large, cuboidal cells that produce pulmonary surfactant.
In week 5, a laryngeal orifice forms, which is a T-shaped opening that leads to the larynx.
Surfactant is a fluid, the name of which is actually short for surface active agent, because it decreases surface
The epithelium inside the larynx turns into laryngeal ventricles, which give rise to the vocal cords.
tension at the blood-air barrier, by lowering the attractive forces between water molecules in the alveoli.
In week 6, the epiglottis forms, and in week 12 the laryngeal opening has its adult shape, as well as thyroid,
This allows the lungs to fill up with air more easily, and it also prevents the collapse of the tiny alveoli during
cricoid, and arytenoid cartilages.
expiration.
Now let’s switch gears and look at the trachea and lungs.
The fourth and final stage of lung development is the alveolar stage, and it lasts from week 36 to about eight
During week 4, two tracheoesophageal ridges form and grow towards one another, ultimately fusing into a years after birth. So, the lungs continue to develop for quite some time!
septum that divides the foregut into two regions: a posterior esophagus and an anterior lung bud.
The alveolar stage overlaps with the terminal sac stage for four weeks.
The lung bud has an endoderm core, which develops into the epithelial and glandular structures of the trachea
During the alveolar stage, thin walls called septa partition the primitive alveoli, giving rise to many more adult
and lungs, surrounded by visceral mesoderm, which develops into muscles, cartilages, and connective tissue.
alveoli, and the number of respiratory bronchioles also increases.
Now, the lung bud basically just hangs off the foregut, and at its loose end it bifurcates into two bronchial buds.
To put this in perspective—we are born with 20 to 70 million alveoli, and by the age of eight, that number
These bronchial buds give rise to the lungs, which grow and develop inside the pleural cavities. increases to a whopping 300 to 400 million. So feel free to take a deep breath now, because you’ve got the
numbers for it!
The bronchial buds develop into lungs in four stages.
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Oh, and speaking of breathing—fetal breathing movements actually begin before birth, so that the lungs and the
respiratory muscles can learn how to work together.
Since there is no air in the uterus, the fetus breathes in amniotic fluid.
At birth, when the baby takes its first breath, that fluid gets reabsorbed into the pulmonary capillaries, leaving
behind a layer of surfactant on the alveolar cell membranes.
In premature babies, lung function depends heavily on how much surfactant has been produced already by the
time of birth.
Summary
All right, as a quick recap... The respiratory system starts developing during week 4 of pregnancy.
The larynx arises from the fourth and sixth pharyngeal arches, and it is completely formed by the week 12.
The lungs and trachea develop from the lung bud starting in week 4, and the lungs mature in four stages: the
pseudoglandular period, the canalicular period, the terminal sac period and the alveolar period.
During the last two stages, type II pneumocytes secrete alveolar surfactant, which prevents the alveoli from
collapsing during expiration.
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The epithelium proliferates and initially fills up the lumen of the esophagus, turning it into a solid rod of tissue,
but by week 8, a process called recanalization occurs, and the esophagus turns it into the hollow tube we know
and love.
Development of the gastrointestinal system
Under the esophagus, there’s the primitive stomach which starts out as a small dilation of the foregut.
During week 3, the embryo is a flat disc made up of three germ layers: the endoderm, the mesoderm, and the The stomach has a dorsal, or posterior border, and a ventral, or anterior border.
ectoderm.
The dorsal border is anchored to the posterior body wall by a two-layered sheet of mesoderm tissue called the
From the endoderm, which you can think of as being the belly side of this three-layered embryo pancake, a fluid dorsal mesogastrium, and the ventral border is anchored to the anterior body wall by another two-layered
filled bubble called the yolk sac forms and grows alongside the developing embryo. sheet, the ventral mesogastrium.
The digestive system starts forming when the embryo folds along its vertical and horizontal axes—so it rolls up Starting in week 5, the liver grows between the layers of the ventral mesogastrium, and the spleen between the
on itself, and turns into a tubular structure that looks a bit like a little shrimp. layers of the dorsal mesogastrium.
Folding also pinches the yolk sac, sort of like squeezing a balloon through a ring, so a part of it goes inside the The dorsal border of the stomach grows a lot faster than the ventral boder and forms the greater curvature of
embryo and forms the primitive gut tube. the stomach, while the ventral border becomes the lesser curvature.
The primitive gut tube is initially sealed off at both ends—the buccopharyngeal membrane at the top separates Alright, so if we switch to a top-down view of this developing stomach, we see that as it grows, it undergoes a
the tube from the primitive mouth, and the cloacal membrane at the bottom separates it from the primitive 90-degree, clockwise rotation along its length, pulling the dorsal mesogastrium and ventral mesogastrium with
anus. it.
This tube is divided into three parts, based on the arterial blood supply. This moves the greater curvature to the left side of the body, and the lesser curvature to the right side, and the
stomach now has an anterior and a posterior face.
The first portion is the foregut, and it's nourished by the celiac artery.
As the stomach rotates, the ventral mesogastrium becomes the lesser omentum.
The middle portion, the midgut, is nourished by the superior mesenteric artery.
The dorsal mesogastrium grows longer and bends as the stomach rotates, forming a peritoneal cavity derivative
For a short while, the midgut communicates with the yolk sac through the vitelline duct, which is eventually
called the omental bursa between the stomach and the posterior body wall.
incorporated into the umbilical cord.
The omental bursa communicates with the great peritoneal cavity through a small opening known as the
Finally, there’s the last portion, the hindgut, which is nourished by the inferior mesenteric artery.
omental foramen.
The hindgut ends with the cloaca, which is the primitive common drainage site for the urinary, genital, and
The omental bursa grows and fills with peritoneal fluid, developing two projections: the upper recess, which
digestive systems.
extends behind the developing liver, and the lower recess, which extends downwards over the developing
The foregut gives rise to the superior part of the digestive tube—up to and including the first half of the intestines.
duodenum, as well as the liver, the gallbladder, and the pancreas.
Eventually, the sheets of dorsal mesogastrium that form the lower recess fuse and form the greater omentum.
At the very top of the foregut, starting at the buccopharyngeal membrane, there’s the primitive pharynx, which
Finally, the stomach rotates once more, but this time in a frontal plane—so imagine looking at it from the front
is initially just five sets of symmetrical pharyngeal arches.
now.
These pharyngeal arches turn into various bones, muscles, and cartilages of the head and neck, and the last two
This final rotation repositions the superior end of the stomach, which will become the cardia sphincter, to the
arches give rise to the final pharynx.
left, and a little bit lower, while the inferior end, the future pylorus, moves to the right, and a little higher.
Below the pharynx, the foregut gives rise to the esophagus.
Below the stomach, there’s the developing duodenum.
In this region, there’s an outpouching of endoderm called the lung bud, and it sprouts from the anterior wall of
The first two sections of the duodenum derive from the last part of the foregut.
the foregut.
The rotation of the stomach turns the duodenum into a C-shaped loop, with the middle of the C on the right
During week 4, the tracheoesophageal septum forms a barrier that separates the lung bud from the foregut; the
side.
anterior compartment develops into the trachea and lungs, and the posterior compartment develops into the
esophagus. The last portion of the foregut also has tiny tissue buds that grow quite large and develop into the liver, the
gallbladder, and the pancreas.
The esophageal epithelium and glands derive from the foregut endoderm, whereas the esophageal muscles
derive from the surrounding mesoderm. The liver bud, also known as the hepatic diverticulum, gives rise to the liver, the gallbladder, and the biliary duct
system.
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This bud forms inside the ventral mesogastrium, and extends into the septum transversum—a sheet of The left one third of the transverse colon, the descending colon, sigmoid colon, and upper part of the anal canal
mesoderm that separates the developing heart from the midgut. derive from the hindgut, which begins after the caudal limb of the midgut and extends to the cloacal membrane.
The liver bud separates into two parts: a larger, superior portion that becomes the liver, and a smaller, inferior The lower portion of the anal canal derives from the primitive anus, or proctodeum, which is a pit of ectoderm
part that becomes the gallbladder. that forms just below the cloacal membrane.
Hepatocytes of the liver are derived from endoderm of the foregut, and they start producing bile during the Also, during week 4, the urorectal septum forms, and it separates the cloaca into an anterior urogenital sinus
week 12. and a posterior anal canal, which are covered by the urogenital membrane and the anal membrane,
respectively.
Kupffer cells, on the other hand, are derived from the mesoderm, and are special macrophage cells that play a
role in local immune defense. At the end of week 7, the separation is complete and the anal membrane ruptures, so that the anal canal is now
continuous and opens in the tail-region of the embryo.
Hematopoietic tissue also develops from mesoderm and starts forming red blood cells during week 6.
The liver functions as the major hematopoietic organ up until the last month of pregnancy, when the bone Summary
marrow takes over.
Now, with the pancreas, there are actually two pancreatic buds, a ventral bud and a dorsal bud, and the two All right, as a quick recap… the digestive tract and associated organs develop from the primitive gut tube.
eventually unite to give rise to a single organ.
Because the abdominal cavity doesn’t grow as fast as the developing organs, the intestinal loops protrude into
The dorsal bud appears first and forms the body, the tail and most of the pancreatic head. the umbilical cord during week 6, but they go back into the body by week 10.
The smaller ventral bud unites with the dorsal bud when the duodenum rotates, and it gives rise to the rest of Initially, the tube is sealed off by the buccopharyngeal membrane superiorly and the cloacal membrane
the pancreatic head. inferiorly, but the membranes disappear, and continuity is established between the gut tube and the mouth at
the top, and the anus at the bottom.
The pancreas begins secreting insulin during week 10.
The midgut gives rise to the third and fourth sections of the duodenum, as well as the jejunum and ileum, which
are parts of the small intestine, as well as the cecum, appendix, ascending colon and the proximal two thirds of
the transverse colon, which are parts of the large intestine.
Now, taking a more three-dimensional view of the midgut, it lengthens a lot over a short period of time, and the
embryo’s abdominal cavity becomes too small to hold it all in.
So, what happens is that the primary intestinal loop (the first loop of the intestines) herniates through the
vitelline duct and develops inside the umbilical cord.
This is called physiologic gut herniation, and it lasts until week 10.
The primary intestinal loop protrudes inside the umbilical cord like a bobby pin, with a superior mesenteric
artery growing between the two limbs of the loop: the cranial limb of the primary intestinal loop initially
develops above the superior mesenteric artery, and the caudal limb of the primary intestinal loop develops
below the superior mesenteric artery.
First, the loop rotates 90 degrees counterclockwise, around the axis of the superior mesenteric artery, and
moves the cranial limb to the right side of the artery, and the inferior limb to the left, like a key inside a lock
that’s turned counterclockwise.
The cranial limb becomes very convoluted and will give rise to the future jejunum and ileum; whereas the caudal
limb develops a small dilation that eventually develops into the cecum and appendix.
In week 10, when the abdominal cavity is big enough for the loop to go back inside the body, the loop rotates a
final 180 degrees, and moves into the abdominal cavity.
This rotation is such that the formerly caudal limb ends up framing the developing small intestine loops above
and to the right, giving rise to the ascending colon and the right two thirds of the transverse colon.
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Around week 5, the metanephros develops, and it forms the permanent kidneys—so for a couple of weeks, the
metanephros and mesonephros coexist.
Development of the renal system The metanephros forms in the pelvic region.
First, intermediate mesoderm near the mesonephric duct differentiates into metanephric mesoderm,
The renal system starts developing during week 4 of intrauterine life. sometimes called the metanephric blastema.
At this point, the embryo is made up of three primitive germ layers: the ectoderm, the mesoderm and the The metanephric mesoderm produces growth factors that travel to the mesonephric duct; in response, the duct
endoderm. sprouts a small bud called the ureteric bud, which is connected to the mesonephric duct through the ureteric
stalk.
The mesoderm also has three parts: the paraxial mesoderm, which flanks the embryo's future vertebral column;
the intermediate mesoderm, which is just lateral to the paraxial mesoderm; and the lateral plate mesoderm, Over time, the ureteric bud lengthens and it secretes growth factors that causes the metanephric mesoderm to
which is the most lateral of all. grow.
The intermediate mesoderm on either side of the embryo condenses to form a cylindrical structure called the This is called reciprocal induction, because the metanephric mesoderm and the ureteric bud promote each
urogenital ridge. other’s growth.
This ridge runs parallel to the embryo’s future vertebral column, and it gives rise to both the urinary and genital Eventually, the ureteric bud reaches the metanephric mesoderm and grows into it, like two lovers running
systems. (albeit very slowly) towards one another.
The portion of the urogenital ridge called the nephrogenic cord develops into the urinary structures. The metanephric mesoderm surrounds the end of the ureteric bud, leaving just the ureteric stalk uncovered.
Now, during the development of the urinary system, there are three sets of structures that emerge from the The ureteric stalk lengthens and forms the ureter around week 6.
nephrogenic cord, and they form in a craniocaudal fashion—from head to tail-end.
The ureteric bud within the metanephric mesoderm divides in half to form the renal pelvis during weeks 7 and 8,
The first structure to emerge from the nephrogenic cord is the pronephros, which appears in the neck region of then each half divides again later to form two major calyces.
the embryo at the beginning of week 4.
These divisions continue until the major calyces, the minor calyces, and finally, the millions of collecting tubules
The pronephros consists of the pronephric duct and the nephrotomes in front of it. have all taken shape.
The pronephric duct is basically a pipe that runs down the length of the nephrogenic cord, and the nephrotomes The cells in the collecting tubules deliver a signal to the surrounding metanephric mesoderm that the collecting
are small chunks of tissue that break off from the nephrogenic cord. system is in place, triggering the formation of the nephrons.
However, the pronephros doesn’t produce urine, and regresses by the end of week 4. The nephrons are the basic functional unit of the kidneys, and they start forming during week 8.
Before the pronephros completely disappears, a second set of structures called the mesonephros appears in the Each newly-formed collecting tubule is surrounded by a cap of metanephric mesoderm.
thoracic and upper lumbar region of the nephrogenic cord.
Cells in the collecting tubules (which come from the ureteric bud) signal the nearby metanephric mesoderm to
The mesonephros has a mesonephric duct and mesonephric tubules in front of it. form round cell clusters called metanephric vesicles.
The mesonephric duct develops off of the pronephric duct, making it longer so that it reaches all the way to the The vesicles elongate and bend into S-shaped tubes, which are similar to the mesonephric tubules.
cloaca, which is the last part of the primitive digestive tract.
One end of the tube connects with the collecting tubules and that part becomes the distal convoluted tubule.
So for a short while, the urinary and digestive system share a common exit.
The other end of the tube forms the proximal convoluted tubule.
Just like the nephrotomes, the mesonephric tubules break off as chunks of tissue from the nephrogenic cord.
The proximal convoluted tubule forms a little cup called Bowman’s capsule, which will hold clump of capillaries
The mesonephric tubules are hollow, S-shaped tubes. that arise from branches off of the aorta, to form the glomerulus.
On one end, they connect to the mesonephric duct, and at the other end, the tubule forms a cup shape called a The portion in between the distal and proximal convoluted tubules lengthens and gives rise to the loop of Henle.
Bowman’s capsule around a clump of capillaries called a glomerulus.
Around week 10, these nephrons start producing urine, and at that point, the metanephros takes over as the
This primitive structure extracts fluid from the capillaries and the fluid flows down the duct to form urine, which permanent kidney.
drains through the mesonephric duct into the cloaca.
As the permanent kidneys develop, they move up from the pelvis to assume their adult position.
This system is in place until week 10, when the permanent kidneys take over and the mesonephros regresses.
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Initially the kidneys are nourished by internal iliac arteries that branch off from the aorta, but as the kidneys
ascend, the aorta forms branches at higher and higher levels to supply them with blood.
When the kidneys reach their final home in the upper abdomen, the renal arteries form, and the lower branches
degenerate.
Rewinding a bit, while the kidneys are forming, the bladder and urethra are developing as well.
The process begins in week 4, when a wall of tissue called the urorectal septum forms in the cloaca.
The urorectal septum splits the cloaca into a posterior anal canal for the digestive tract, and an anterior
urogenital sinus for genital and urinary structures.
The top portion of the urogenital sinus stretches out to form the primitive bladder.
Now, remember, the ureters develop from the ureteric stalk, and they open into the mesonephric ducts, which
drain urine into the bladder.
During weeks 5 and 6, the mesonephric ducts are slowly absorbed into the bladder to form the smooth part of
the bladder wall: the vesical trigone.
The vesical trigone is a triangular region that contains the openings of the ureters, as well as the opening of the
urethra.
The middle portion of the urogenital sinus forms the urethra in the females and the prostatic and membranous
parts of the urethra in males.
Finally, the bottom portion of the urogenital sinus grows towards the genital tubercle, forming either the clitoris
or the penis.
Summary
All right, as a quick recap… The nephrogenic cord, which is part of the urogenital ridge, gives rise to three sets of
foundational renal structures: the pronephros, the mesonephros, and the metanephros.
The metanephros are the permanent kidneys, and they form from the metanephric mesoderm, which forms the
nephrons, as well as from the ureteric bud, which forms the collecting system.
The metanephric mesoderm forms a small part of the bladder, but the urogenital sinus is responsible for most of
the bladder and the entire urethra starting with the fourth week.
The permanent urinary system is mature enough to secrete urine starting around week 10 of intrauterine life.
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The surface epithelial layer of each gonad thins out to become the tunica albuginea.
Later on the medullary cords develop into three ductal structures inside the testes: the seminiferous tubules,
Development of the reproductive system straight tubules, and the rete testis.
Of the three, the primordial germ cells settle down in the seminiferous tubules, and that’s where they mature
Reproductive system development is the series of events that an embryo goes through to sexual differentiate into spermatogonia and lay dormant for a number of years.
into a male or female with regard to the gonads, genital ducts, and external genitalia.
During puberty, the spermatogonia awaken and start dividing over and over again to give rise to sperm, the
The process starts at conception - when the gametes, the sperm and oocyte, fuse into a single cell that has male gametes.
either XX sex chromosomes in a female or XY sex chromosomes in a male - establishing the genetic sex of the
embryo. mDuring week 8, some cells in the wall of the seminiferous tubules differentiate into Sertoli cells.
Through the first 5 weeks of development however, sexual development is basically identical for both sexes. Sertoli cells surround the primordial germ cells, and secrete anti-mullerian hormone.
At that point, the embryo is made up of three primitive germ layers: the ectoderm, the mesoderm and the In addition, cells between the seminiferous tubules differentiate into Leydig cells, and they secrete testosterone.
endoderm.
Antimullerian hormone and testosterone masculinize the rest of the male reproductive tract.
The mesoderm also has three parts: the paraaxial mesoderm, flanking the embryo's future vertebral column, the
intermediate mesoderm which is just lateral to it, and the lateral plate mesoderm which is the most lateral of all. Now, in a female, since there’s no Y chromosome to secrete testis-determining factor, the undifferentiated
gonads develop into ovaries.
The intermediate mesoderm on both sides of the embryo condenses into two cylindrical structures called the
urogenital ridges. In this case, the primitive sex cords also extend towards the center of the gonad, but they degenerate soon
after.
Each urogenital ridge runs parallel to the embryo’s future vertebral column, and organizes into a cylinder of
mesoderm called the nephrogenic cord. The surface epithelium proliferates once more, and forms a second set of projections called cortical cords.
Most of the nephrogenic cord goes on to form urinary structures, but a strip of it in the middle gives rise to the The cortical cords rearrange to form nests of follicular cells that surround the primordial germ cells.
gonads in males and females.
A primordial germ cell and its ring of follicular cells make up a primordial ovarian follicle, and inside it, the
This portion that gives rise to the gonads is called the genital or sometimes gonadal ridge. primordial germ cell differentiates into an immature oocyte during fetal life.
The genital ridge has a mesoderm core and is covered with epithelium. The immature oocytes are halted in the first prophase of meiosis 1 until puberty, at which point they turn into
secondary oocytes, the female gametes.
Gonad development, interestingly enough, starts in a tissue outside the embryo called the yolk sac - which is
lined with endoderm cells, and connects to the embryo through the vitelline duct. The rest of the reproductive tract acquires female characteristics in the absence of testosterone.
Early in development, some endoderm cells from the wall of the yolk sac differentiate into primordial germ cells, The differentiation of the gonads leads to the phenotypic differentiation of the genital ducts and the external
and they begin to migrate - physically move - along the vitelline duct, to the primitive digestive tract, and finally genitalia.
to the dorsal mesentery - a sheet of tissue that anchors the digestive tract to the posterior body wall.
The genital ducts are initially undifferentiated, tubular structures that run down the embryo’s back inside the
From there, the primordial germ cells march along the dorsal mesentery until they reach the genital ridge - two nephrogenic cords on either side of the embryo.
arriving there around week 6. The primordial germ settle in the epithelium.
The first is the mesonephric, or Wolffian duct, which gives rise to the male reproductive duct system.
and they send out chemical signals to the cells in the genital ridge, which makes them self-organize into an
The second is the paramesonephric, or Mullerian duct, which is lateral to the mesonephric duct and gives rise to
undifferentiated gonad - which can still develop into either testes or ovaries.
the female reproductive duct system.
The epithelial layer of the gonad then forms primitive sex cords, which are epithelial projections that penetrate
These ducts start in the thoracic and upper lumbar region, and continue down the embryo’s back, until they
inwards, into the mesoderm layer of the gonad.
open into a part of the cloaca called the urogenital sinus, which gives rise to urinary tract structures and the
Around week 7, sex chromosomes start expressing genes that determine gonadal differentiation. external genitalia of both sexes.
In a male, genes in the sex-determining region of the Y chromosome - or SRY, for short - code for a protein called In males, mullerian inhibiting factor makes the paramesonephric - or mullerian - ducts degenerate into two
testis-determining factor, which initiates the development of testis. vestigial bodies called the appendix testis.
The primitive sex cords mature into medullary cords, that grow longer and carry the primitive germ cells deeper The mesonephric ducts, on the other hand, grow longer under the influence of testosterone, and form the
into the mesoderm. reproductive ducts outside the testis.
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The efferent ductules look a bit like the teeth of a comb, and they connect the intratesticular straight tubules to Finally, there’s one more step in the development of the reproductive system.
the epididymis.
The gonads have to descend to their adult positions, in both males and females!
The epididymis is where sperm go to mature after they’ve been produced in the testes.
Starting with males, the testes initially develop near the anterior abdominal wall, but they are anchored by the
After the epididymis, there’s the vas deferens, through which sperm will be released during ejaculation. gubernaculum, a fibrous cord that attaches to the bottom of the scrotum by a fibrous cord called the
gubernaculum.
An accessory gland called the seminal gland develops from each vas deferens, and it secretes a nourishing fluid
for the travelling sperm. The gubernaculum starts to shorten, pulling the testis down towards the scrotum through the inguinal canal.
At the end of each vas deferens, below the opening of the seminal glands, there’s an ejaculatory duct, which The inguinal canal forms when a projection of peritoneum called the processus vaginalis herniates through the
opens into the urogenital sinus which forms the male urethra. abdominal body wall.
In females, on the other hand, the ovaries don’t make testosterone, so the wolffian ducts degenerate; and the By week 12, the testes reach the inguinal canal, and move towards the scrotum.
ovaries don’t make mullerian inhibiting factor either - so the paramesonephric ducts persist.
On their way, they pull the vas deferens and the testicular artery and vein with them through the inguinal canal.
In their upper regions, the two paramesonephric ducts form the fallopian tubes. These structures eventually form the spermatic cord.
In their lower regions, the ducts fuse and form the uterovaginal primordium, which is a tubular structure from The journey is usually over by the last month of pregnancy, and the abdominal muscle layers that came along
which the uterus, the cervix, and the upper third of the vagina develop. form the layers of the scrotum.
The lower two thirds of the vagina develops from the urogenital sinus when the external sex organs Now, in female embryos, there’s also a gubernaculum that attaches the inferior part of the ovary to the future
differentiate. labia majora, and it shortens to pull the ovaries down the same way it would if they were testis.
The external sex organs also go through an undifferentiated stage, during which the lowermost portion of the However, when the uterus forms, the middle of the gubernaculum attaches to it and separates in a superior
urogenital sinus opens up in the genital region. portion known as the cranial genital ligament, which becomes the ovarian ligament, anchoring the ovaries
slightly above and on either side of the uterus.
Flanking the opening on either side, there are two sets of symmetrical folds: the urethral folds, and the
labioscrotal swellings. The inferior portion, called the caudal genital ligament becomes the round ligament, connecting the uterus to
the labia majora.
Above the opening, there’s a small bit of tissue called the genital tubercle, which first turns into a primordial
phallus for both sexes.
Summary
The differentiation of the external genitalia into male external sex organs starts when testosterone levels begin
to rise.
All right, as a quick recap: The reproductive system goes through an undifferentiated phase of development,
An enzyme called 5-alpha-reductase, which can be found in many tissues in our body, including the skin of the which is the same for both sexes, but in week 7, the primitive structures differentiate into male or female sex
external genitals, converts testosterone into a dihydrotestosterone, it’s more potent form. organs, according to the sex chromosomes that the baby has had since conception.
Starting with week 9, dihydrotestosterone masculinizes the external sex organs of male embryos. First, the gonads develop into ovaries or testicles, and the differentiation of the gonad acts on the rest of the
reproductive tract, which gives rise to correspondent male or female sex organs.
The urethral folds fuse on the midline and form the penile urethra.
Both the ovaries and the testis initially develop in the abdomen, but descend during pregnancy to reach the
The primordial phallus grows longer, and its tip forms the glans penis, while its body gives rise to the body of the pelvic cavity or the scrotum.
penis, which encloses the penile urethra.
The labioscrotal swellings fuse as well, giving rise to the scrotum.
For genetically female embryos, in the absence of testosterone, the urethral folds remain unfused and form the
labia minora.
The labioscrotal swellings form the labia majora, and only fuse in their anterior portion to give rise to the mons
pubis.
The primordial phallus shrinks and turns into the clitoris.
All in all, phenotypical differentiation is complete around week 12 - so this is about as early as you could tell the
sex of an unborn baby.
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First, there’s endochondral ossification, in which case mesenchymal cells first differentiate into chondrocytes
that build a hyaline cartilage model which then turns into bone.
Development of the axial skeleton When that happens, the center of this cartilage model is the primary ossification center, and blood vessels enter
it, bringing in nutrients and osteoblast cells which help build bone - B for build, as well as osteoclast cells that
collapse bone, C for collapse.
The fetal skeleton starts developing soon after gastrulation, which is when the trilaminar disc with ectoderm,
mesoderm and endoderm layers are formed. The osteoblasts replace the chondrocytes at the primary ossification center and start to replace the cartilage
with bone.
There are two parts to the skeleton - the axial skeleton, which includes the bones in the skull, the vertebrae, the
rib cage, and the sternum, and the appendicular skeleton, comprising of the pelvic and shoulder girdle, as well as As the bones grow thicker and more sturdy, osteoclasts start to chomp away in the middle of the bone, making
the bones in the limbs. it more porous - and this is how bone marrow appears.
The bones in the axial skeleton mostly derive from the mesoderm layer, except for some bones in the skull Most of the bones in our body form through endochondral ossification, except for the clavicles, and bones in the
which come from the ectoderm. skull like the parietal and frontal bones, as well as the maxilla, mandible, the nasal bone and parts of the
temporal and occipital bones.
All the bones in the appendicular skeleton derive from the mesoderm.
These exceptions form through intramembranous ossification, which is when mesenchymal cells differentiate
During week 3, the embryo transitions from a flat organism to a more tubular creature, by folding along its
into osteoblast cells which create the primary ossification center and start building bone without any cartilage
longitudinal and lateral axes.
model.
At the same time, a solid rod of mesoderm called the notochord forms on the midline of the embryo.
As before, blood vessels reach the center of the primary ossification center, which already has osteoblasts, and
Above the notochord, the ectoderm invaginates to form the neural tube - an early precursor for the central bring in nutrients.
nervous system.
Okay, now let’s start at the very top and take a look at the development of the skull.
This is the embryo's first symmetry axis, and the mesoderm on either side of the neural tube differentiate in 3
The skull has two main parts: the neurocranium, which is the hard shell protecting the brain, and the
distinct portions: immediately flanking the neural tube, there’s the paraxial mesoderm.
viscerocranium, which makes up the structures underlying the face.
Next, there’s the intermediate mesoderm, and finally, the lateral plate mesoderm.
The neurocranium is itself divided into two parts: First, there’s the membranous neurocranium, which forms
The intermediate mesoderm gives rise to the urinary and genital systems, while the paraxial mesoderm and through intramembranous ossification, and makes up the flat bones of the skull.
lateral plate mesoderm work together to give rise to most of bones and muscles in our body.
These flat bones surround the brain - you can think of a protective helmet: anteriorly, there’s the frontal bones,
The first step in skeletal development is when paraxial mesoderm segments into blocks of mesodermal tissue above - the parietal bones, posteriorly, a part of the parietal bones and the occipital bone, and laterally, a special
called somites, which are made up of lots of cube-shaped cells. little spot where the parietal, occipital, and temporal bones meet - like three old friends.
Next, the somites divide into three different cell populations: the sclerotome, which forms the vertebrae, the rib Then there’s the cartilaginous neurocranium – or the chondrocranium, which forms through endochondral
cage, and the lower part of the occipital bone, the dermatome, which forms the skin of the back, and the ossification and gives rise to the base of the skull – or the bony floor underneath the brain.
myotome, which forms the back, limb and intercostal muscles.
The chondrocranium accounts for the rest of the occipital and the temporal bones, as well as the sphenoid and
Meanwhile, lateral plate mesoderm splits into parietal mesoderm and visceral mesoderm layers. ethmoid bone.
The parietal mesoderm forms the early limb buds, the bones of the pelvic and shoulder girdle, and the sternum, The viscerocranium arises from the first pharyngeal arches - which are the first of five paired bars of mesoderm
while the visceral mesoderm helps form organs like the heart, lungs, and organs in the gastrointestinal tract. that arch towards one another along the midline of the embryo.
So, the axial skeleton derives mainly from paraxial and lateral plate mesoderm cells. These arches have a core of mesenchymal cells which originate as neural crest cells.
But, in the head region, another group of cells derived from the ectoderm layer, called neural crest cells, As far as facial bones go, the first pharyngeal arch forms the upper and lower jawbone, as well as the
contributes to the development of the skull. cheekbones and the temples of the skull.
Before they can develop into bone, all these different kinds of cells first transform into multipotent Just to go back to our helmet analogy - the viscerocranium would make up the faceguard protecting our mouth
mesenchymal cells, through a process called epithelial to mesenchymal transition. and nose from damage. And this faceguard is slightly curved, to remind you that the bones come from the first
pharyngeal arch.
The resulting mesenchymal cells have special properties, such as the ability to migrate to different locations and
give rise to different organs and tissues in our body - including bones. When a baby’s born, the skull bones are not fused and it looks a bit like a jigsaw puzzle where the pieces haven’t
quite snapped together.
Now, from here on, there’s two ways that fetal bones can form.
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Between the bone plates, there are long, narrow, fibrous sutures that hold the skull together. The sternum develops separately from the rest of the ribcage, emerging from parietal mesoderm in the
embryo’s ventral body wall.
Wide openings called fontanelles exist at the points where more than two bones come into contact: there’s 6 of
them in total, 2 on either side, and two larger ones on top - the anterior fontanelle, between the parietal and
frontal bones, and the posterior fontanelle between the occipital and parietal bones.
These sutures and fontanelles provide the skull with a tiny amount of flexibility, which makes it easier for the
large head to squeeze through the vaginal canal during childbirth.
After the baby is born, the fontanelles close up one by one - the last one to close is the anterior fontanelle, and
it’s often referred to as the soft spot on a baby’s head. It closes at around 18 months.
During week 4 of development the spinal vertebrae develop, and it happens when the somites undergo a
process called resegmentation.
First, each somite separates in two populations of cells: a rostral, or top population, and a caudal, or bottom
group.
Next, these two populations of cell separate and the bottom population of one somite fuses with the top
population of the ensuing somite.
This gives rise to new segments of tissue formed by cell populations deriving from two separate, adjacent
somites.
The sclerotome cells in these segments surround the notochord and spinal cord they transform into
mesenchymal cells and give rise to the vertebrae through endochondral ossification.
As the vertebrae take shape, the neural tube develops into the spinal cord, from which spinal nerves emerge
through the spaces between the vertebrae.
In front of the spinal cord, however, the bodies of the vertebrae grow and make the notochord degenerate for
the most part.
However, between the vertebrae, the notochord persists as the nucleus pulposus of the intervertebral discs.
During week 5, small clusters of mesenchymal cells called costal processes emerge from the lateral sides of each
vertebrae.
In the thoracic region, these processes grow really long and form the ribs.
Finally, the sternum develops from the parietal mesoderm layer in the anterior body wall of the embryo.
Here, the parietal mesoderm organizes as a pair of vertically-oriented cartilaginous bars on either side of the
midline, which eventually fuse and differentiate into the three parts of the sternum: the broad manubrium at
the top, the main body of the sternum, and the small xiphoid process at the bottom.
Summary
All right, as a quick recap. The axial skeleton arises from mesodermal and neural crest cells, which turn into
mesenchymal cells.
Mesenchymal cells then give rise to bone, either through endochondral ossification, or through
intramembranous ossification.
The bones and cartilage of the spinal vertebrae, as well as the ribcage, derive from the somitic sclerotome.
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Cells from the dorsomedial lip of the somite (the top right layer of cubes here) mix with some cells from the
ventrolateral lip in the opposite corner of the cube (the bottom left) to form a new, mixed tissue called
dermomyotome.
Development of the muscular system
Dermomyotome cells further differentiate into dermatome and myotome cells, which turn into the dermis layer
of the skin and into muscles, respectively.
The muscular system starts taking shape when the embryo is just a flat little pancake made up of two layers: the
epiblast on the dorsal, or back, side, and the hypoblast on the ventral, or front, side. Now, fast forwarding a bit, the muscles of the myotome start to develop.
A line called the primitive streak appears on the epiblast “back” of this two-layered creature. One way to categorize the muscles is according to their innervation.
Cells migrate along the primitive streak during gastrulation, leading to a now three-layered embryo pancake, Each myotome develops along with a spinal nerve that emerges from the spinal cord and branches off into a
with each layer containing germ cells that form organs and tissues of the body. ventral and a dorsal division.
The ventral, or bottom, germ layer is called endoderm, the dorsal, or top, germ layer is called ectoderm, and the This divides the myotome into two muscle-forming regions: the first is the epimere, which engenders the
layer in between these two is called mesoderm. muscles of the back, and it’s innervated by dorsal rami, or back branch, of spinal nerves.
Collectively, these germ cells produce all of the organs and tissues in the body. The second is the hypomere, which engenders the muscles of the limbs and body wall, and it’s innervated by the
ventral rami, or front branch, of the corresponding spinal nerve.
During week 3, the embryo transitions from a flat organism to a more tubular creature by folding along its
longitudinal and lateral axes. Another way to categorize muscles is according to their origin.
At the same time, a solid rod of mesoderm called the notochord forms on the midline of the embryo. Lateral to the somite, there’s an area called the lateral somitic frontier that separates the somites from the
parietal mesoderm flanking them.
Above the notochord, the ectoderm invaginates to form the neural tube, an early precursor of the central
nervous system. Like a border between two countries, this line splits embryonic mesoderm into two distinct territories: the
primaxial domain and the abaxial domain.
This is the embryo's first symmetry axis, and the mesoderm on either side of the neural tube differentiates into
three distinct portions: immediately flanking the neural tube there’s the paraxial mesoderm; next, there’s the The primaxial domain originates from somites around the neural tube, so it’s mainly composed of paraxial
intermediate mesoderm; and finally, the lateral plate mesoderm. mesoderm.
Between the cells of the lateral plate mesoderm, small gaps appear and coalesce to form the intraembryonic Primaxial mesoderm cells receive signals from the neural tube and the notochord, and they differentiate into
coelom, a cavity inside the embryo’s body. back, shoulder, and intercostal muscles.
This cavity separates the lateral plate mesoderm into two layers: a parietal layer that’s in contact with the The abaxial domain originates from parietal mesoderm and migrating somite cells that cross over the lateral
ectoderm, and a visceral layer that’s in contact with the endoderm. somitic frontier.
The paraxial and lateral plate mesoderm will become the skeletal muscles in our body. Abaxial mesoderm cells receive signals from the parietal mesoderm and differentiate into abdominal wall
muscles, limb muscles, and one muscle in the neck called the infrahyoid muscle.
Before the mesoderm cells develop into skeletal muscle, they first organize into cell blocks called somites.
Finally, the last little muscle type we didn’t mention is the syndetome, which arises between the sclerotome and
Somites arise in pairs from a combination of paraxial mesoderm cells and mesenchyme, which is a soupy fetal
myotome.
tissue containing pluripotent cells.
The syndetome forms the tendons, which are flexible collagen cords that attach skeletal muscles to bones.
Around day 20 of development, somites begin to form in the occipital region of the embryo, which is at the base
of the head. Early muscle cells are called myoblasts, and they merge into long spindles of muscle tissue called myofibrils.
Somites continue to form cranio-caudally, or from head-to-tail end of the embryo, with about three pairs These myofibrils bundle together and fuse to form cylindrical skeletal muscle fibers.
forming each day.
Here’s a visual: if you held a bunch of straws together in your hand, the individual straws would be the
Up to 40 somite pairs form by the end of week 5. Some degenerate, while the rest go on to form bone and myofibrils, and the whole bunch would represent one muscle fiber.
muscle structures.
Cardiac muscle is closely related to skeletal muscle in structure, but differs a bit in that it can contract and relax
Each somite undergoes a split, with cells from the ventral portion forming sclerotome, creating the vertebrae continuously and automatically.
and the ribs.
Visceral mesoderm cells wrap around the primitive heart and differentiate into cardiac myoblasts, which will
then form cardiac muscle.
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Finally, there’s the smooth muscle. Smooth muscle lining the gut tube develops from visceral mesoderm cells,
whereas smooth muscle cells that line the arteries derive from visceral mesoderm cells as well as from neural
crest cells.
Some smooth muscles, like the ciliary muscles that allow the pupils to expand and contract, and the smooth
muscle of the mammary and sweat glands, are derived from ectoderm.
To remember these ectoderm exceptions, think about a woman named Vectoria, who is sweating (sweat glands)
and has dilated pupils (pupillary muscles) as she runs into a battlefield with a giant breast plate (mammary
glands).
Summary
All right, as a quick recap: during development, mesoderm cells differentiate into the majority of the body’s
muscular tissues, forming the skeletal and cardiac muscle and most of the smooth muscle.
The only muscles that don’t arise from mesoderm are the smooth muscles of the pupils, and the sweat and
mammary glands, which instead arise from ectoderm.
Development of the limbs
Limb buds appear at the end of the fourth week of development. They develop in a proximal-to-distal fashion,
lead by the apical ectodermal ridge, a region of ectoderm on the distal border of the limb. Fingers and toes
form when the cells of the apical ectodermal ridge start to die. Limb musculature and bones derive mainly
from primitive streak mesoderm.
Pharyngeal arches, pouches, and clefts
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Early in development, the embryo is a flat, disc-shaped organism made up of three layers of pluripotent cells The second arch also forms the stapes, a tiny ear bone (the smallest bone in the body) which works with the
called germ layers: an inner layer, called endoderm, a central layer, called mesoderm, and an outer layer, called malleus and incus to help transmit sound to the inner ear.
ectoderm.
Muscles from the second pharyngeal arch mainly control facial movement and expression.
These three specialized cell layers give rise to all the organs and tissues in the body.
Some second arch muscles, like the posterior belly of the digastric and the stylohyoid muscle, also help us with
By week 4 of development, the embryo takes on a more recognizably human form—but to be honest, it still swallowing.
looks more like a shrimp than a baby.
Other muscles derived from this arch are the tiny stapedius muscles, which anchor the stapes of the ears.
At the cranial (head) end of this little shrimp-like creature, a set of structures called the pharyngeal apparatus
begins to develop, consisting of pharyngeal arches, clefts, and pouches. Third pharyngeal arch structures are innervated by the glossopharyngeal nerve.
The pharyngeal apparatus starts forming around weeks 4 and 5, when six little bars of mesoderm, the There’s actually only two structures that originate from third arch: the rest of the hyoid bone, and one muscle of
pharyngeal arches, sprout from the primitive pharynx. the throat (the stylopharyngeus) which helps with swallowing.
The pharyngeal arches develop in a craniocaudal fashion—meaning they form at the head and continue Now, remember, because the fifth arch does not form anything, our last pharyngeal arches are the fourth and
developing towards the tail end of the fetus. sixth.
These paired, symmetrical bumps are numbered from 1 to 6—it's important to note that the fifth arch either These are both innervated by branches of the vagus nerve: the superior laryngeal branch innervates the fourth
never forms, or it quickly regresses, so it doesn’t develop into any structures. arch’s structures, and the recurrent laryngeal branch innervates the sixth arch’s structures.
Between the five pharyngeal arches, four pharyngeal clefts form and cover the external part of the The fourth and sixth arches don’t form any bones, but they do work together to form the laryngeal cartilages.
corresponding arch with ectoderm cells, while four pharyngeal pouches line the internal part of their
The fourth pharyngeal arch gives rise to muscles in the mouth, pharynx, and larynx: the levator palatini, which
corresponding arches with endoderm.
prevents food from entering the respiratory tract while we swallow; the pharyngeal constrictors, which squeeze
The components of the pharyngeal apparatus develop into various head and neck structures, and sometimes food down the esophagus; and the cricothyroid muscle, which tenses the vocal cords to produce sound.
multiple arches join together to give rise to a single structure.
The sixth arch gives rise to the rest of the intrinsic muscles of the larynx that help us speak.
Each pharyngeal arch, with its associated pouch and cleft, carries its own cranial nerve that innervates the
Three of the pharyngeal arches work together to form the tongue, which speaks to the complexity of this
structures that develop from that arch.
unique, muscular organ.
The first pharyngeal arch is mainly associated with everything we need to chew.
The anterior two-thirds of the tongue start out as a bud from the floor of the first arch.
Structures from this arch are innervated by the trigeminal nerve–more specifically, its mandibular branch.
We can remember this because when we chew with structures formed by the first arch, we might end up biting
In terms of bones, it gives rise to the maxilla (which forms the upper jaw) and the mandible (which forms the the anterior portion of the tongue!
lower jaw).
The posterior one-third comes from buds of the third and fourth arches; these arches form most of the
Two small portions of the mandible will give rise to the incus and the malleus bones of the middle ear, which structures in the pharynx, which is where the posterior portion of the tongue is.
resemble an anvil and a hammer and transmit sound vibrations from the eardrums.
When it comes to structures formed by the pharyngeal arches, there’s a lot to remember, so we put together an
The first pharyngeal arch also forms part of the temporal bones as well as the zygomatic bones or cheekbones. extensive mnemonic to help you recall this important information more easily. Here, we’ve got five different
To remember that, you might think of Ziggy Stardust— who we can all agree had striking cheekbones! characters at the circus, who represent the five pharyngeal arches.
Muscles that come from the first pharyngeal arch include muscles that help us chew (the temporalis, masseter, Let’s imagine a little boy named Billy who’s happily chewing gum while visiting the circus.
and pterygoid muscles); a muscle that blocks out noises from chewing (the tensor tympani); and some of the
Billy’s the first character, so let’s say he’s the first arch, and he’s chewing gum because the muscles and bones of
muscles that help us swallow (the tensor veli palatini, the mylohyoid muscles, and the anterior belly of the
the jaw come from arch one.
digastric).
His name, Billy, is on the front of his shirt to remind us of the anterior belly (Billy/belly!) of the digastric.
The posterior belly of the digastric will be formed by the second arch—so there’s an example of pharyngeal arch
teamwork. Billy’s favorite circus game is the strength tester, which has a giant hammer and a giant anvil at the bottom,
representing the malleus and incus (those bones in the ear).
The second pharyngeal arch forms structures that will be innervated by the facial nerve; a lot of these structures
help us make facial expressions. Billy smashes the anvil with the hammer, and his bubble gum pops. The sound startles him and he tenses up,
reminding us of tensor tympani and tensor veli palatini.
In terms of bones, we have the hyoid bone (specifically the lesser horns and the upper portion) and the styloid
process of the temporal bone. Next, Billy meets a clown with a big frown, who, coincidentally, is also named Billy.
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Billy the clown is our second character, so he represents the second arch, and his frown reminds us of the The ventral portion of the third pouch becomes the primitive thymus, which will later descend down to the
muscles of facial expression. chest.
Billy the clown’s name is printed on the back of his shirt, reminding us of the posterior belly of the digastric. The ventral portion of the fourth pouch becomes the ultimopharyngeal body, a pouch-like embryological
structure containing cells which differentiate into parafollicular or C cells of the thyroid.
Billy the clown works part-time in the rodeo; one of his feet is still stuck in a stirrup, reminding us of the stapes
and stapedius muscles, and he’s carrying a bunch of horseshoes, reminding us of the horseshoe-shaped hyoid C cells produce calcitonin which lowers blood calcium.
bone.
The thyroid itself develops from the endoderm at the base of the tongue, independent of the pharyngeal
Billy heads over to the circus’ main attraction, two giraffes, one with three spots and one with four spots, both apparatus.
with long, beautiful necks. So, these giraffes (our third and fourth characters) remind us that the third and fourth
arches give rise to the pharynx. As the embryo grows, the thyroid descends down the neck, and the parathyroid glands will actually latch onto it
as it passes by.
The three-spotted giraffe likes to wear accessories like horseshoes, reminding us that the third arch also
contributes to the horseshoe-shaped hyoid bone. Cells from the ultimopharyngeal body migrate into the thyroid as it continues its journey downwards to rest at
the base of the neck.
The three-spotted giraffe also like to wear a stylish scarf, which represents the stylopharyngeus muscle.
Meanwhile, the four-spotted giraffe is busy eating leaves, reminding us that the fourth arch gives rise to the Summary
muscles that help move food down the esophagus.
All right, as a quick recap… The pharyngeal arches are derived from mesoderm and give rise to many of the
Suddenly, the giraffe starts choking—the leaves went down the wrong way, into the windpipe! That’s because
bones and muscles in the head and neck.
the four-spotted giraffe has a problem with its levator palatini muscle (which normally prevents food from going
down the wrong tube), so it ends up with a cricket in its larynx, which represents the cricothyroid muscles. The pharyngeal clefts derive from ectoderm, forming structures in the ear canals.
The master of ceremonies at the circus is a supremely talented six-year-old mime! Our sixth, silent, six-year-old The pharyngeal pouches arise from endoderm cells, and these form parts of the ears, as well as the early tonsils,
character reminds us that the sixth arch gives rise to the muscles in the larynx that produce sound. The only and many portions of the parathyroid glands and thyroid.
exception is the cricothyroid cricket that’s stuck in our four-spotted giraffe’s windpipe.
The talented mime performs surgery on the giraffe to remove the cricket, and puts a long, hard cast around the
giraffe’s neck, which represents the laryngeal cartilages which come from the fourth and sixth arches.
Okay, enough playing around at the circus. Let’s look at the pharyngeal pouches and clefts.
Separating the pharyngeal arches on the outside of the embryo are four pharyngeal clefts, layered with
ectoderm cells.
The second and fourth clefts fade as the embryo grows, while the first cleft works closely with the first
pharyngeal pouch to form the ear.
Because the clefts are on the outside, the first cleft gives rise to the external auditory meatus (ear canal) and
also forms the ear drums.
The first pharyngeal pouch, which is on the inside, gives rise to a long, thin cavity that expands to form the
internal auditory meatus or middle ear.
As the embryo grows, a small portion of the cavity remains narrow, becoming the eustachian tube between the
auditory canal and the nasopharynx.
Cells lining the second pharyngeal pouch multiply and migrate to form the primitive tonsils.
The third pouch and fourth pouch are very similar in that they divide into a dorsal and ventral portion.
Development of teeth
The dorsal portion of the third pouch becomes the inferior parathyroid glands, while the dorsal portion of the
fourth pouch becomes the superior parathyroid glands.
The mandible and maxilla grow during the sixth week of development to make space for teeth to grow within
These glands create parathyroid hormones which help regulate calcium and phosphate levels in the blood. them. The teeth originate from 10 dental buds in each jaw, which grow during the 3rd month of fetal
42 | P a g e
development. The permanent teeth are also derived from these buds, however they remain inside until six
years age, when they grow and push out the deciduous primary teeth.
Development of the brain

Development of the ear
The developing brain is divided into three sections: prosencephalon, mesencephalon, and rhombencephalon,
also known as forebrain, midbrain, and hindbrain, respectively. The prosencephalon will give rise to the The otic placodes are the first signs of the developing ear. They are thickenings of the surface ectoderm on
telencephalon, the future cortex and basal ganglia, and the diencephalon, which will evolve into the optic cup, each side of the rhombencephalon, and develop into otic vesicles, or otocysts. These will later give rise to
the inner ear, and divide into a ventral part, generating the saccule and cochlear duct, and a dorsal
thalamus, hypothalamus, and mammillary bodies. The mesencephalon will become the tectum, cerebral
component, making the utricle, semicircular canals and endolymphatic duct. The middle ear has an
aqueduct, red nucleus, the substantia nigra and the crus cerebri. The rhombencephalon will generate the endodermal origin, the auditory tube, tympanic cavity and epitympanic recess, and a mesenchymal origin,
metencephalon, the future pons and cerebellum, and the myelencephalon, which will become the medulla the ossicles. The auricle instead develops from six mesenchymal proliferations, termed auricular hillocks,
oblongata. and the external auditory meatus develops from first pharyngeal cleft ectoderm.
Development of the eye

Development of cranial nerves and autonomic nervous system
The eyes develop around the fourth week as outpocketings of the forebrain, called optic vesicles. They
The 12 cranial nerves are all present by the fourth week of development. The olfactory nerve develops from therefore have a neuroectodermal origin. The vesicles continue their development by invaginating and forming
the telencephalon, the optic nerve from the diencephalon, the oculomotor and trochlear nerves from the a double-walled optic cup. They will generate the retina, optic nerve, ciliary and iris epithelium, and pupil
mesencephalon, the trigeminal, abducens, facial, and vestibulocochlear nerves from the metencephalon,
constrictor and dilator muscles. The lens has an ectodermal origin, coming from the lens placode, a thickening
and the glossopharyngeal, vagus, accessory and hypoglossal nerves from the myelencephalon. The adrenal
gland has an ectodermal origin relative to the medulla, deriving from neural crest cells, and a mesodermal of surface ectoderm overlying the optic cup. The choroid and cornea have the same mesenchymal origin.
origin for what concerns the cortex.
Development of the spinal cord
The spinal cord is part of the central nervous system and is derived from neural crest cells. When the neural
tube closes and neuroepithelial cells differentiate into neuroblasts, they move to different areas which then
lead to development of different parts of the spinal cord. The grey matter of the spinal cord is made from
neuroblasts in the mantle layer, whereas the white matter of the spinal cord is made from neuroblasts in the
marginal layer in the outermost layer of the spinal cord.
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Human Development Days 1-4

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Embryology-Early development/Organ system development

Around day 12, the decidua undergoes the decidual reaction.

The next type of mesoderm is intermediate mesoderm.

However, the yolk sac is still poking out in the mid-section.

This means that the remaining arches are numbered 1, 2, 3, 4, and 6.

This also contributes to the closing of the ductus arteriosus.

The labioscrotal swellings fuse as well, giving rise to the scrotum.

The primordial phallus shrinks and turns into the clitoris.

Development of the limbs

Pharyngeal arches, pouches, and clefts

Development of the brain

Development of the eye

Development of the spinal cord

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