Third Week of Development:

Trilaminar Germ Disc

By
AIAH Lebbie
M.B.Ch.B, FCS (ECSA)
Implantation site
Dorsal aspect of an 18-day embryo
 Gastrulation: Formation of Embryonic
Ectoderm, Mesoderm and Endoderm
• Gastrulation is the process by which the three
germ layers - ectoderm, mesoderm, and
endoderm are formed
• main event occurring in the third week
• begins with formation of the Primitive streak
on the surface of the epiblast
– narrow groove with slightly bulging regions on
either side and primitive node at the cephalic end
• Cells of the epiblast migrate toward the
primitive streak
• Upon arrival these cell become flask shaped,
detach from epiblast and slip under the streak
→ invagination
• FGF8 controls both the migration and
specialization of the cell in to mesodermal
cells
– FGF8 regulate migration by down regulation
cadherin which usually bind epiblast cells
– Regulates specification by regulating Brachyury (T)
expression
• Some invaginated cells displace the hypoblast →to
form endoderm
• Some cells come to lie between the epiblast and newly
formed endoerm → forming Mesoderm
• Cells remaining in the epiblast form the Ectoderm
• the first set of migrating cells also form the prechordal
plate between the tip of the notochord and
buccopharyngeal membrane
• With proliferation the cells spread laterally and in
cranially to extend beyond the disc and contact
extraembryonic mesoderm covering the yolk sac and
amnion
• Cranial spread on either side of the prechordal
plate which is formed by the first set of
migrating cells
• Prechodal plate will later induce formation of
forebrain
Formation of the Notochord
• Formed from prenotochordal cells
• During invagination these cells migrate cranially to
prechordal plate
• become intercalated in the hypoblast so that
• for a short time, the midline of the embryo
consists of two cell layers that form the
notochordal plate
• the hypoblast is replaced by endoderm cells
moving in at the streak
• notochordal plate detach from the endoderm to
form the definitive notochord
• The notochord forms the basis for axial skeleton
• The buccopharyngeal membrane is at the
cranial end of the embryonic disc while the
cloacal membrane is at the caudal end
• Both membranes consists of tightly adherent
ectoderm and endoderm cells with no
intervening mesoderm
• When the cloacal membrane appears, the
posterior wall of the yolk sac forms a small
diverticulum that extends into the connecting
stalk → allantois or allantoenteric
diverticulum
• The allantois is rudimentary but may be
involved in abnormalities of bladder
development
 Establishment of the Body Axes
• Body Axes
• Anteroposterior
• Dorsoventral
• left–right
• Body axes are established before and during
the period of gastrulation
• cranial end of the embryo before gastrulation
• anteroposterior axis is signaled by cells at the
anterior (cranial) margin of the embryonic disc in
an area known as Anterior Visceral Endoderm (AVE)
• AVE expresses several genes essential for head
formation
– transcription factors → OTX2, LIM1, and HESX1
– Cerberus
• The primitive streak itself is initiated and
maintained by expression of nodal, a member of
TGFβ
• bone morphogenetic protein 4 (BMP4) and
fibroblast growth factor (FGF) favor
ventralization to contribute
– kidneys (intermediate mesoderm)
– blood, and body wall mesoderm (lateral plate
mesoderm)
• cranial mesoderm is dorsalized into notochord,
somites, and somitomeres when chordin
(activated by the transcription factor
Goosecoid), noggin, and follistatin produce by
the Node antagonize the activity of BMP4
• Therefore the node is called the organizer
• Later, these three genes are expressed in the
notochord and cause neural induction in the
cranial region
• HNF-3β maintains the node and later induces
regional specificity in the forebrain and midbrain
areas
• Left–right sidedness, also established early in
development
• Many genes are involved in establishing left
sidedness but the establishment of right sidedness
is not well understood
Fate Map Established During Gastrulation

• Migrating epiblast
are mapped and
their fates are
determined
 Growth of the Embryonic Disc
• initially flat and almost round
• gradually becomes elongated with broad
cephalic and a narrow caudal end
– continuous migration of cells from the primitive
streak region in a cephalic direction
• Expansion occurs mainly cephalic region
• primitive streak region remains more or less
the same size
• Invagination and migration of epiblastic cell in
cephalic and lateral direction continues till the
end the 4th week
• Then primitive streak shows regressive
changes, rapidly shrinks, and soon disappears
• Differentiation of germ layers :
– Begins in the middle of the third week in the
cephalic region
– In the caudal region differentiation begins at the
end of the 4th week
• Thus while differentiation is occurring in the
cephalic region, gastrulation will still be
continuing in the caudal region of the embryo
• This explains why embryonic development
progresses in a cephalocaudal direction
 Clinical pplication
• Teratogenesis Associated with Gastrulation
• The period of gastrulation is highly sensitive to
teratogenic insult because it is the time when
fate maps of various organs are determined
• These developing cells are easily damaged by
teratogens
• Example of high doses of alcohol in early
pregnancy may result in holoprosencephaly →
deficiency of the midline in craniofacial
structures
• Alcohol kills the cell in the anterior midline of
the embryo
– Small forebrain
– the two lateral ventricles often merge into a single
ventricle
– hypotelorism
• genetic abnormalities and toxic insults can also
disrupt gastrulation
– Caudal dysgenesis (sirinomelia) → result from
insufficient mesoderm formation in caudal embryo
• This affect strctures formed from mesoderm
– hypoplasia and fusion of the lower limbs
– vertebral abnormalities
– renal agenesis
– imperforate anus
– anomalies of the genital organs
• Sacrococcygeal teratoma resulting from
remnants of primitive streak
 Situs inversus
• transposition of the viscera in the thorax and
abdomen
• Only slight increase in the incidence of other
abnormalities
• 20% have bronchiectasis and sinusitis due to
abnormality of cilia (Kartagener syndrome).
 Bilaterality Sequence
• Usually do not have complete situs invesus
• May be bilaterally left sided or bilaterally right
sided
• Bilaterally left sided individuals typically
have polysplenia
• Bilaterally right sided individuals have
asplenia or hyposlenia
 Tumors Associated with Gastrulation

• remnants of the primitive streak may persist

in the sacrococcygeal region →
sacrococcygeal teratomasn which is the most
common tumor in newborns
• SCT can also arise from primordial germ cells
that fail to migrate to the gonadal ridge
Further Development of the Trophoblast

Beginning of During the End of

3rd week 3rd week 3rd week
• Tertiary villus is otherwise known as the
definitive placental villus
• Capillaries in tertiary villi make contact with
capillaries developing in mesoderm of the
chorionic plate and in the connecting stalk
• These vessels, in turn, establish contact with the
intraembryonic circulatory system, connecting
the placenta and the embryo
• Hence, when the heart begins to beat in the
fourth week of development, the villous system is
ready to supply the embryo proper with essential
nutrients and oxygen
• The next stage in the development of the
trophoblast consist of the core cytotropholast
penetrating the outer syncytial layer to reach
the maternal endometrium
• establish contact with similar extensions of
neighboring villous stems, forming a thin outer
cytotrophoblast shell
• This cytotrophoblast shell surrounds the
trophoblast entirely and attaches the chorionic
sac firmly to the maternal endometrial tissue
• Villi that extend from the chorionic plate to the
decidua basalis (decidual plate) are called stem
or anchoring villi
• Villi that branch from the sides of stem villi are
free (terminal) villi
• exchange of nutrients and other factors will
occur through the terminal villi
• The chorionic cavity becomes larger
• by the 19th or 20th day, the embryo is attached
to its trophoblastic shell by a narrow connecting
stalk
• The connecting stalk later develops into the
umbilical cord
• The umbilicus forms the connection between
placenta and embryo