AsturiaNOTES

Lecture 1: Neuroembryology
Neuroscience 1: Neuroembryology

The nervous system starts to form at the 3 rd week of life from the ectoderm at the
specialized part called the neuroectoderm/neurectoderm.
 The Notochord forms at the 3rd week of life
o It is the source of inducers
 The inducers seep into the overlying ectoderm and stimulate a
cellular thickening and form the following structures in subsequent
order:
1 Neural plate
a Will indent to form #2
2 Neural groove
a Will deepen to form #3 at the lateral margins
3 Neural fold
a The edges of the neural fold will start to approximate
each other and eventually fuse at the posterior
midline, and then separate with the overlying
ectoderm to form the #4:
i However, before it separates from the
overlying ectoderm, a portion of the neural
folds will also separate from the surface
ectoderm that will NOT move with the neural
tube—but rather—position itself dorsolateral
to the neural tube and this will be called the
neural crest
 Neural crest gives rise to PNS
4 Neural Tube
a Neural tube proceeds rostrally and caudally to form
the anterior and posterior neuropores,
respectively
b Formation of the neural tube from neural plate gives
rise to the brain and spinal cord up to lumbar
levels
c Layers of Neural Tube:
i Ventricular Zone
 Progenitor cells of this layer gives rise
to:
o Neurons
o Glial cells
o Ependymal cells—line
ventricles
ii Marginal Zone
 Contains processes of the cells located
in the ventricular zone
 Does NOT contain nuclei

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Lecture 1: Neuroembryology
Neuroscience 1: Neuroembryology

iii Intermediate Zone

 Formed in between the ventricular and
marginal zones
 Nuclei from ventricular zone move into
this layer with the processes extending
to the marginal zone
iv Mnemonic:
 ―Neural Tube Layers are VIM‖
o The notochord defines the long axis of the developing embryo
o The notochord determine the orientation of the vertebral column
o The notochord also produces cell adhesion molecules (N-CAM or simply,
CAM) so that cells in the overlying notochord will move as a single unit
o In the adult, the notochord persists as the nucleus pulposus/pulpy
nucleus located in the intervertebral disks between the vertebrae

PRIMARY NEURULATION
 All the processes mentioned above: from neural plate to neural tube giving rise
to the CNS (Brain+SC) is called primary neurulation
 Occurs at Day 18-25 AOG

 Therefore, the neural tube is the primitive CNS

o Rostral 2/3—gives rise to the brain
o Caudal 1/3—gives rise to the SC (up to lumbar levels)
o Caudal eminence gives rise to sacral and coccygeal segments

 Neural crest—develops into the PNS

o Derivatives:
 Schwann cells
 Cranial nerve ganglion
 Dorsal root ganglion
 Autonomic ganglion
 Chromaffin cells of Adrenal Medulla
 Pia and Arachnoid of meninges
 Melanocytes

DISORDERS OF THE PRIMARY NEURULATION

Dysraphic Effects—congenital malformation associated with defective neurulation.

Incidence of which can be reduced through supplementation of folic acid

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Lecture 1: Neuroembryology
Neuroscience 1: Neuroembryology

A. Anterior Neuropore Anomalies

1. Anencephaly
 Literally means ―Without Brain‖
 Cause: failure of the anterior neuropore to close
o Anterior neuropore closes at Day 24
o Anterior neuropore closes first before the posterior neuropore
 No neural tube in anterior aspect
 Brain is not formed, meninges are absent and skull, with abnormal fascies
 100% mortality—babies survive at most for 1 week
 No extraordinary measures given: Comfort, love, and prayers  sorry baby love 

2. Encephalocoele—herniation of intracranial contents

 AKA Crania bifidum
 Types of encephalocoele (or encephalocele, whichever)
o Meningocoele—herniation of meninges
o Meningoencephalocoele—herniation of meninges + brain
o Meningohydroencephalocoele—herniation of meninges + brain + part
of ventricular system

3. Arnold-Chiara Malformation
 The congenital herniation of the cerebellar vermis through the foramen
magnum causing pressure on the medulla and cervical spinal cord

B. Posterior Neuropore Anomalies

Posterior neuropore anomalies are collectively known as myeloschisis

1. Spina Bifida—failure of the vertebral arches to form completely and fuse to cover
the spinal cord
 Types of Spina Bifida
o Spina Bifida Occulta
 If there is skin covering the spinal cord
 Minimal defect
o Spina Bifida Aperta
 If there is NO skin covering the spinal cord
o Spina Bifida Cystica
 If there is a cystic mass accompanying the spina bifida
1 The cystic mass is protruding at the area of non-closure that
can be a:
a Meningocoele—meninges + CSF
b Meningomeylocoele—meninges + CSF + spinal
neural tissue (either Spinal Cord or part of the
cauda equina)

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Neuroscience 1: Neuroembryology

i Meningomyelocoele causes loss of

movement or sensation in areas below the
lesion

2. Myelosrachischisis
 Open neural tube at the back
 High mortality
 Prognosis varies on the degree of defect
 There is functional impairment

Preventive measures for all these dysraphic effectsSupplementation of Folic acid

daily (usually 400 micrograms)

SECONDARY NEURULATION

This is the formation of the sacral and coccygeal segments of the spinal cord
that begins on Day 20 and ends on Day 42.
 Gives rise to sacral and coccygeal portions
 Appearance of caudal eminence caudal to the neural tube which enlarges and
cavitates and this joins the neural tube to form a continuous neural canal
o It is in the neck region where the neural fold starts to approximate each
other and eventually form the neural tube during primary neurulation.
 It then proceeds rostrally and caudally along the length of the
embryonic disc
1 There are rostral and caudal openings:
a Rostral opening—the Anterior Neuropore
i Communicates the neural cavity with the
amniotic cavity
ii Closes first because the cervical region/neck is
closer rostrally; Day 24
 When the anterior neuroporecloses, it
forms a membrane called lamina
terminal
b Caudal opening—the Posterior Neuropore
i Connects the caudal neural cavity with the
caudal amniotic cavity
ii Closes after the anterior neuropore at Day 26

DISORDERS OF THE SECONDARY NEURULATION

Disorders of the secondary neurulation are termed to be as Myelodysplasias

 The site of myelodysplasia may be marked with:
o Unusual pigmentation
o Unusual hair growth

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Neuroscience 1: Neuroembryology

o Prominent dimpling of overlying skin

Tethered Cord Syndrome

 Abnormality wherein the conus terminalis and filum terminale are abnormally
fixed to the defective vertebral column thus affecting the exiting spinal
nerves from the cord
 Loss of sensation in the lower extremities
 Urinary Bladder control problems
 The lower back is usually with:
o Tufts of Hair
o Violaceous in color
o Prominent dimple
 It is more symptomatic than spina bifida

BRAIN VESICLES

Primary brain vesicles are formed during anterior neuropore closure (Day
24, 4th week AOG).
 Prosencephalon—forebrain
 Mesencephalon—midbrain
o Contains the mesencephalic flexure (cephalic flexure) that demarcates
the midbrain from the forebrain
 Rhombencephalon—hindbrain (cavity: 4th ventricle)
o Contains the cervical flexure—a slight bend found at the
rhombencephalon-spinal cord junction
o Will form the:
 1 Foramina of Magendie (Midline)
 2 Foraminae of Luschka (Lateral)
 Both will be passageways of CSF
1 If the sylvian aqueduct is small, CSF will be shunted to these
foraminae so quickly creating an obstructing hydrocephalus
 Mnemonic: ―Primary brain vesicles ay parang train because PMR (pnr train hahaha)

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Neuroscience 1: Neuroembryology

Secondary Brain Vesicles—the 3 Primary Brain Vesicles (PBV) divide into 5

secondary brain vesicles (SBV) during 5th week

Figure 1. Primary Brain Vesicles becoming Secondary Brain Vesicles

Note on development of Primary Brain Vesicles:

 Mesencephalon does NOT divide further—it is retained
o Therefore, the a distinction should be when referring to the mesencephalon—
specify with either Primary/Secondary Brain Vesicle
 Prosencephalization
o Process wherein the prosencephalon is divided into the Diencephalon and
Telencephalon via the Telencephalic Flexure
o Diencephalon—the Thalamic family (cavity: 3rd ventricle)
 Adult Derivatives:
1 Thalamus, Epithalamus, Hypothalamus, Subthalamus
2 Pineal gland
3 Retina
4 Optic Nerve
5 Mamillary bodies
o Telencephalon—expands to form the following structure and therefore
becomes the largest part of the brain (cavity: 2 lateral ventricles):
 Adult Derivatives:
1 Cerebral hemispheres—including cortex and medullary
centers
a Lobes (Occipital, frontal, etc)
b Gyri
c Sulci
2 Olfactory system
3 Hippocampus
4 Corpus striatum
5 Lamina Terminalis

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Neuroscience 1: Neuroembryology

6 Basal Ganglia
 The telencephalic vesicles become the primordia of the cerebral
hemispheres. And the adult derivative: Cerebral Cortex
o Failures of Prosencephalization—failure of the prosencephalon to
undergo cleavage:
 Alobar prosencephaly—no discernable lobes develop
1 You cannot demarcate where is the temporal lobe from the
occipital from the etc etc
 Semilobar holoprosencephaly—there is some degree of separation;
occipital areas are usually prominent
 Fates of other secondary brain vesicles:
o Mesencephalon—midbrain (cavity: sylvian aqueduct)
o Metencephalon:
 Pons
 Cerebellum
o Myelencephalon—medulla oblongata

Choroid Plexus—blood vessel inside the ventricle, responsible for the production of
CSF(?)
 During the development of the ventricles, the blood vessel that is outside will dig
inside bringing with it meningeal layers (PAD)
o This is why meningioma can originate inside the ventricles

There are certain infections acquired by the pregnant mother that can cause
congenital nervous system (especially neural tube defects) defects to the baby  :
 TORCH
o Toxoplasma
o Others (Syphilis by Treponema pallidum)
o Rubella virus
o Cytomegalovirus
o Herpes simplex virus

DEVELOPMENT OF THE SPINAL CORD

The spinal cord is formed from the caudal portion of the neural tube
 Neural canal—becomes the central canal of SC

Transverse Differentiation of Primitive Neural Tube

 Neural tube initially exists as a single layer of pseudostratified columnar
epithelium with intense proliferative activity
Again, three layers: VIM
 Ventricular Zone (Ependymal Zone)—Inner Layer
o Cellular layer
 Marginal Zone—Outer Layer

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Neuroscience 1: Neuroembryology

o Acellular layer, ONLY process

 Intermediate Zone (Mantle Zone)—Middle layer
o Cellular layer

The Intermediate Zone

 AKA Mantle Layer
 Grows asymmetrically
 Contains the Sulcus Limitans
o A demarcation separating the proliferating cells from:
 Dorsal Half
 Ventral Half
o Dorsal to the sulcus limitans are structures that will comprise the alar plate
 Alar plate is the posterior portion of the ventricular zone
1 AP will give rise to the Dorsal Root Ganglion (DRG)
a DRG is sensory in function
b DRG receives processes from the pseudounipolar
neurons forming the dorsal root of the spinal
nerve
o Ventral to the sulcus limitans are structures that will comprise the basal
plate
 Basal plate is the anterior portion of the ventricular zone
1 BP gives rise to the anterior horn
a Anterior horn is motor in function
b Anterior/ventral gray horn sends axons to form
the ventral root of the spinal cord to supply a
specific myotome level
o How about the marginal zone?
 Will become the white matter of the SC

The Spinal Cord

 Each cord segment will be supplying a specific area of the skin called a dermatome
 As the anterior/ventral gray horn is developing, it will form the anterior root of
the spinal nerves which would supply a specific group of muscles called myotome
of that specific cord segment
o As the cord is developing, the spine is also developing
 However, at 2 nd trimester and at birth, the SC is shorter than the
vertebra indicating faster growth rate of the bony vertebra
1 There is a discrepancy in length of the cord and the length of
the vertebra, so much so that the cord is almost at the level of
L2 only
a Therefore, the first sacral nerve will have to travel
a longer way to reach S1
 At birth, the SC is at L1
 In the adult, the SC is between L1-L2

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Neuroscience 1: Neuroembryology

Nerve Termination
 This phenomenon is biochemically dictated.
o Structures derived from the neural crest contain in their surface integrins
which recognize specific molecule in the connective tissue at a specific
dermatome level, which in turn contains fibronectin/laminin containing a
specific amino acid sequence.
 This mechanism enables the integrins to know where to terminate

DEVELOPMENT OF THE BRAINSTEM

 Consists of the myelencephalon, pons, and mesencephalon
o Myelencephalon—gives rise to medulla oblongata
 Has a portion which is similar to the spinal cord and a portion where
the neural cavity opens to become the 4th ventricle
1 Spinal-cord like medulla—all structures dorsal to the sulcus
limitans such as the sulcus gracilis and nucleus cuneatus
are alar plate-derived and have sensory function
a The gracilis is for conscious proprioception on the
legs
b The cuneatus would be conscious prioprioception
of UE and the trunk
 Upper 1/3 of Medulla—the cavity there opens to form the 4th
ventricle
1 Because of the opening of the cavity to become the ventricle,
the alar plate becomes rotated dorsolaterally and becomes
lateral to sulcus limitans
2 As for the basal plate, it will now become medial to the
sulcus limitans
 Lower 2/3 of Medulla—alar is now posterior/dorsal while basal—
ventral/anterior
 Cranial Nerves of Medulla
1 CN 7,9, 10—forms the nucleus solitarius for taste
2 Descending nucleus of CN 5 –for facial sensation
3 CN 9-12 can be found in the Myelencephalon

DEVELOPMENT OF THE CEREBELLUM

 Arises from the rostral portion of the rhombic lip (alar structure that forms part
of the wall of 4th ventricle)
o Rhombic lip is:
 Proliferative; as it starts to row further, it would meet with the rhombic
lip of the other side and cover the posterior surface of the 4 th ventricle
to give rise to the cerebellum
 Caudal part gives rise to the inferior olivary, cochlear, and
pontine nuclei

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Neuroscience 1: Neuroembryology

 Has Inner white matter, outer gray matter

 Cells from the intermediate zone would migrate using the radial glial cells as
scaffold to hold on to while they migrate external to the marginal zone to form the
external granular layer
o From this layer, the following will be formed:
 Granule cells
 Stellate cells
 Basket cells
 From the original intermediate zone, the cells would also migrate but they migrate
outward and would give rise to the deep cerebellar nuclei and purkinje cells
 The posterolateral fissure develops first before the primary fissure
o Posterolateral fissure—divides the cerebellum into the:
 Flocculonodular lobe
 Corpus cerebelli
o Primary fissure—divides the corpus cerebelli into:
 Anterior lobe
 Posterior lobe

DEVELOPMENT OF THE THALAMIC FAMILY (DIENCEPHALON)

 The mature diencephalon cannot be seen externally because it is covered by the

cerebral cortex. Thus, one would have to will have to dissect the brain sagitally
or coronally
 The diencephalon is largely derived from the alar plate
 The diencephalon gives rise to:
o Epithalamus
o Hypothalamus
o Thalamus
 Development occurs in an “outside-first” sequence (Lateral nuclei
develop first, medial ones last)
1 First neurons to undergo final cell division migrate to the
outermost portion of the thalamus
a Generated first are the lateral nuclei:
i Geniculate nuclei
ii Lateral nuclei
iii Ventral nuclei
b Generated last are the medial nuclei:
i Dorsomedial nucleus
2 Radial glia serves as a guide for migration

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Lecture 1: Neuroembryology
Neuroscience 1: Neuroembryology

DEVELOPMENT OF THE CEREBRAL CORTEX (TELENCEPHALON)

 Development pattern is “inside-out”

 The outer gray has 6 layers
 Formation of the cortical plate at interface of marginal-intermediate zones
o Marginal zone gives rise to layer 1 of cerebral cortex
o Cortical plate gives rise to layers 2-6 of cerebral cortex
 Formation of the subplate—a narrow region internal to the cortical plate
o Subplate and intermediate zone gives rise to subcortical white matter
 1st trimester—hallmark of a normal brain to have gyri+sulci/fissures
o Due to the limited space in the skull, when brain tissue encounters
resistance—it would fold forming gyri and sulci
o More neurons buried inside the sulci and fissure
o 1st trimester fissures:
 Interhemispheric fissures
 Sylvian fissure
 Central sulcus
o 8th month fissures:
 Secondary sulcus
o 3rd trimester fissures:
 Tertiary/all sulci are formed
 Cerebral cortex is the higher centers for critical thinking, imagination,
analysis, etc
 Abnormalities:
o Lissencephaly—failure of gyri to form creating a smooth surfaced cortex
o Pachygyria—unusually large gyri
o Microgyria—unusually small gyri
o Scizencephaly—abnormal patterns of sulcal and gyral development with
unilateral or bilateral clefts in cerebral hemisphere

VENTRICULAR SYSTEM
 Normally, should be patented so that the CSF can circulate
 Any abnormality in the ventricular system is called hydrocephalus
o Treated by shunting the flow of the CSF
 Otherwise, the trapped CSF will cause pressure in the developing
neurons and they atrophy
o Obstructive Non-communicating Hydrocephalus
 When there is atresia of the cerebral aqueduct, the CSF canot
circulate, there will be dilation proximal to the obstruction
1 Due to: Congenital aqueductal stenosis
o Non-obstructive Communicating Hydrocephalus
 No obstruction but there is abnormality in the transfer of the CSF from
the subarachnoid to the venous system

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Neuroscience 1: Neuroembryology

PARAMETERS IN BRAIN ORGANIZATION

 Density or Number of Neurons
o Neurons—terminally differentiated and thus, they will not undergo mitosis
 6 months AOG:
1 There is overproduction of neurons. After which, there will be
selective apoptosis of neurons that are not good/useful
 Pattern of Axon and Dendrite Branching
o Age 2-3 y/o—complete neurons with dendritic and axonal branching
 Pattern of Synaptic Contacts
o Occurs throughout life
o Neurons are always open to new learning—synaptic contacts can be
fashioned/remodeled—Lumosity

o Factors affecting synaptic stabilization

 Critical period refers to time period when these types of plastic
changes occur—varies from region to region
1 Ex: Baby with congenital cataract or severe myopia of left ey
a As the baby grows, the impulses from the right eye
would have to establish synaptic stabilization in the
visual centers in the cortex
b But since the left eye is severely myopic, whatever
stimulation it receives is not enough to send synaptic
contact to the cerebral cortex
c If this is not treated early, the entire visual cortex will
be taken over by the good eye so much that if later,
corrective lenses are given, they’re going to be
useless since the visual cortex has been taken over by
the synaptic contacts made by through the right eye
Synaptic Development
 Parallels cellular proliferation and migration
 Maximal period is during six months after birth
o Vulnerable to:
 Perinatal hypoxia
 Malnutrition
 Environmental toxins

Myelination
 Peak: From six months after birth to first year of life
 Continues into adulthood
 Motor and sensory tracts mature early
 Affected by:
o Leukodystrophy
o Phenylketonuria
o Malnutrition

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Neuroscience 1: Neuroembryology

o Impaired Lipid Metabolism

Plasticity
 Alteration in selective neuronal death, axonal simplification and retention of
transient axonal branches and synapses that would otherwise be lost
 Therefore, the developing bran is not as vulnerable to injury as the mature brain
o Critical period: The period of time during which plastic changes can occur. If
the critical period is over, then changes become permanent

-end-
References

1. Lecture notes by RAsturiano (A-2019) from the lecturer

2. Transcription notes by Carmella Agcaoili (A-2019)
3. Super subsec notes 2015

Downloadable for free at: www.theelusivedoktora.wordpress.com

For any corrections you may find, content or otherwise, email me at:
ram.ustmedicine@gmail.com

-THANKS-

AsturiaNOTES
By RAsturiano
#TheElusiveDoktora

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