NEUROEMBRYOLOGY BY

DR JAIYEOBA-OJIGHO JENNIFER
EFE

Corrected(slide 59 and 62)and final

slides
Introduction
EARLY EMBRYOGENESIS
 Fertilization
 Bilamnar germ disc
 Trilaminar germ disc
 NEURULATION
Fertilization and cleavage
Bilaminar germ disc
Trilaminar germ disc
Domains of ectodermal germ layer
 Major derivatives of the ectodermal germ layer.

 The ectoderm is divided into three major domains the

 Surface ectoderm (primarily epidermis),

 The neural tube (brain and spinal cord)

 Neural crest (peripheral neurons, pigment, facial cartilage).

CONT
At the tissue level, neurulation occurs in four stages
(i) Transformation of the central portion of the embryonic
ectoderm into a thickened neural plate
(ii) Shaping and elongation of the neural plate
(iii) Bending of the neural plate around a medial groove
followed by elevation of the lateral folds
(iv) Closure result in neural tube.
Note:
The term “neurulation” specifically refers to stage (iii)
but
 The name is commonly used when describing all of the
events that occur between neural induction and neural
tube closure.
STAGES OF NEURULATION
 The first stage(key factors)
 The uncommitted or naïve ectoderm becomes committed to
the neural lineage.
 As a result of Neural induction.
 Inducing substances, secreted by the underlying prechordal
plate and the cranial portion of the notochordal plate,
 Responsible for ectodermal commitment to a neuronal
lineage by the overlying epiblast cells
What is the principal early morphological response of the
embryonic ectoderm to neural specification?
 increase in the height of the cells (Neuroectoddestined to
become components of the nervous system
 evident as a thickened neural plate visible on the medial
dorsal surface of the early embryo
A mid-sagittal section through the embryo at the time of gastrulation.
The embryo is shaped like a disc suspended between the amniotic and
yolk sac cavities. Cells migrating through the node have formed the
notochord and prechordal plate in the midline and these structures will
induce the overlying ectoderm to form the neural plate.
NEURAL CREST CELLS
 These are cells that lie along the lateral edges of the
neural tube

Cross sections through the forming neural tube.A, Neural plate. B, Neural fold.
C, Neural folds apposed.D, Neural tube complete. (Neural crest before and
after it sexit from the neural epithelium is shown in green.)
NEURAL CREST CELLS
DERIVATIVES OF NEURAL TUBE
DERIVATIVES OF NEURAL TUBE
Layers of neural tube for cell differenciation

 AT first the wall is lined by a single layer of cells. These differenciate into
germinal(matrix), mantle and marginal layer
 Cells of the germinal layer give rise to nerve cells ,neuroglial and more germinal cells
Mantle layer consist of developing nerve cells and neuroglia cells
The marginal layer contain no nerve cells.
It provides a framework for the mantle layer in which the processes of nerve cells
can develop
Layers of neural tube for cell differenciation
KEY NOTES ABOUT THE MANTLE LAYER
 The mantle layer divides into a ventral part(basal lamina)
form motor structures
 also a dorsal part (alar lamina) forms sensory
structures
These are seperated by a groove called sulcus limitans
 spinal cord- alar lamina forms posterior grey column/
basal forms ventral grey column
 medulla, pons and midbrain- efferent nuclei of cranial
nerves develop in basal lamina/afferent nuclei in alar
lamina
The alar lamina in mesencephalon forms the colliculi,
red nuclues and substantia nigra
THE BRAIN FLEXURES
 I earlier talked about flexures that arises and gives the structures of the brain their orientation
 The telecephalic flexures occurs much later between the telencephalon and diencephalon
Formation of a typical neuroblast

STARTS with a germinal cell from the germinal layer to the mantle layer to become
apolar neuroblast which develops into bipolar neuroblast having two processes which
later forms the unipolar neuroblasts having one process
The main process of the multipolar neuroblast grows into the marginal layer and
becomes axon of a nerve cell
It may remain in the CNS or grow out as an efferent nerve fibre of peripheral nerve
The smaller processes are called dendrites
At first the cytoplasm is homogenous. Later nissil granules make their appearance
After their formation, they loose the ability to divide
Cont.
 Neuroglial cells are also formed from germinal cells of
the matrix layer
They are called glioblast
They migrate into the mantle and marginal zones as
medulloblasts
 they differenciate into astroblasts and oligodendroblasts
Which further forms astrocytes and oligodendrocytes
Microglial cells are not from the neural tube, migrate with
blood vessels into it
Mesodermal in origin
Nerve fibres that remain within the CNS becomes
ensheated by oligodendrocytes
Those that leave the CNS are ensheated by Schwann cells
which is a derivative of neural crest cells
Spinal cord
Spinal cord

 the cavity is in form of a dorsal lateral cleft. Lateral walls are thick, the roof
( dorsal) and the floor (ventral) are thin
 the wall of the tube divides into a matrix, mantle and marginal

Stage 3
The mantle zone grows faster in the ventral part and becomes thicker than
the dorsal part
As a result it becomes compresses.as development continues, the mantle
layer divides into a dorsal alar lamina and a ventral basal lamina

The basal part develops into structures that are motor in function
While the alar part develops into structures that are sensory in function
Cont.
 with continued growth
of the mantle layer , the
spinal cord acquire its
definitive shape.
With growth of the alar
lamina , the dorsal part
of the cavity (roof)
becomes obliterated, the
posterior median
septum is formed
The ventral part of the
cavity becomes the
central canal.
Further projection of the
basal lamina causes it to
project on either side
leaving a furrow ,the
anterior median fissure
 Cont.
 Nerve cells of basal lamina becomes neurones of
anterior grey column while those of alar lamina
becomes neurones of posterior grey column.
 axons of neurones of posterior grey column travel
upward in the marginal layer and form ascending tracts
of the spinal cord
 Axons of cells developing in various parts of the brain
migrate to the marginal layer and form descending
tracts of the spinal cord
 Both ascending and descendng tracts form the white
matter of the spinal cord
 the white matter further divides into anterior, lateral
and posterior white column.
Cont.
 In vertebrates the ganglion is a cluster of neural
bodies outside the central nervous system. A spinal
ganglion, for instance, is a cluster of nerve bodies
positioned along the spinal cord at the dorsal and
ventral roots of a spinal nerve.

 Spinal ganglia are formed from dorsal nerve roots

 Dorsal nerve roots are formed from axons of cells
that develop from the neural crest
Development of the medulla
MEDULLA
 The medulla develops from the myelencephalon
 Early development is similar to that of the spinal cord
 The apperance of the sulcus limitans divides each lateral
wall into a dorsal or alar lamina and a ventral or basal
lamina
 Subsequently the thin roof becomes greatly widened as a
result the alar comes to lie dorsolateral to the basal lamina .
 Which makes both laminae to be in the floor of the
developing fourth ventricle
 Cells developing in the lateral part of each alar lamina
migrate ventrally
 They get to the marginallayer overlying the ventrolateral
aspect of the basal lamina
Cont
 These cells constitute the caudal part of the bulbo-
pontine extension
 They develop into the olivary nuclei
 The remaining cells develop into the sensorynuclei of the
cranial nerves (sensory cranial nerve nuclei) related to the
medulla
 The motor nuclei of these nerves are derived from the
basal lamina
 Initially the nerve cells of the laminae are at first grouped
in accordance with their function
 Subsequently some of these nuclei migrate ventrally from
their primitive position in the floor of the fourth ventricle
 The white matter is composed of fibres constituting the
ascending and descending tracts that pass through the
medulla
Cranial nerve nuclei of medulla
Embryology of the pons
 The pons arises from the ventral part of the
metencephalon
 It also receives a contribution from the alar lamina of the
myelencephalon in the form of the cranial part of the
bulbo- pontine extension
 This extension comes to lie ventral to the metencephalon,
and gives rise to the pontine nuclei
 Axons of cells in these nuclei grow transversely to form the
middle cerebellar peduncle
 As in the myelencephalon, the roof of the metencephalon
becomes thin and broad.
 The alar and basal laminae as thus oriented as in the
medulla.
Cranial and caudal parts of
bulbopontine extension
Embryology of the pons
 As in the myelencephalon, the roof of the metencephalon becomes thin and
broad.
 The alar and basal laminae are thus oriented as in the medulla
 The lateral part of each alar laminae (rhombic lip) becomes specialized to
form the cerebellum
 The ventral part of the alar lamina gives origin to the sensory cranial nuclei
of the pons
 WHILE the basal gives rise to motor cranial nerve nuclei of the pons.
 the nuclei derived from the basal and alar laminae lie in the dorsal or
tegmental part of the pons
 the ventral part of the pons is constituted by :
1. Cells of the bulbo pontine extension derived from the alar lamina of the
myelencephalon that form the pontine nuclei
2. Corticospinal and corticobulbar fibres that descend from the cerebral
cortex and pass through this region on their way to the medulla and spinal
cord
3. Some fibres from the cerebral cortex terminate in relation to the pontine
nuclei.
Development of medulla and pons
Cranial nerve nuclei of pons
CEREBELLUM

The cerebellum consists of grey matter and white matter:

Grey matter – located on the surface of the cerebellum. It is tightly folded,
forming the cerebellar cortex.
White matter – located underneath the cerebellar cortex. Embedded in the white
matter are the four cerebellar nuclei (the dentate, emboliform, globose, and fastigi
nuclei).
CEREBELLUM
 CEREBELLUM
 THE cerebellum at first consist of the usual matrix layer,
mantle layer and marginal layer.
Some cells of the mantle layer migrate into the marginal
layer to form the cerebellar cortex
 cells that do not migrate into cortex forms the dentate,
emboliform, globose and fastigial nuclei

A cerebellar peduncle is a nerve tract that permits

communication between the cerebellum and the other parts
of the central nervous system
Superior peduncles-axons cells from dentate nuclues
Middle peducles-axons cells from pontine nuclei
Inferior peduncles- fibres that grow into the cerebellum from
spinal cord and medulla
 Dentate, emboliform, globose and fastigial nuclei are
cholinergic neurones.
 NEURAL TUBE DEFECTS
Anencephaly, encephalocoele, and spina bifida are the three
most common forms of NTDs.
ANENCEPHALY
 is the most severe of these lesions.
 The neural tube opens at the region of the brain
 The exposed brain tissue degenerates.
ENCEPHALOCOELES
 as a result of non closure of the neural tube, neural tissue
may lie outside the cranial cavity or vertebral canal.
 When it happens in the region of the brain is called
encephaloceles.
 When it occurs in the spinal region, is called myelocoele
A. An encephalocoele diagnosed by ultrasound. Notice the cursors
identifying the small amount of extruded brain tissue through the cranial
defect. B. The infant after delivery.
 Cont.
Non fusion of the neural tube is associated with non
closure of the cranium or vertebral canal
That of the vertebral canal is refereed to spinal bifida
Types of spina bifida
DEVELOPMENT OF THE MIDBRAIN
Cerebrum and cerebral cortex
Introduction

Development of cerebral vesicles

Development of choriod plexus/fissure

Develoment of corpus straitum

Development of cerebral cortex

The cerebrum is comprised of two different types of tissue – grey matter and
white matter:
Grey matter forms the surface of each cerebral hemisphere (known as the
cerebral cortex), and is associated with processing and cognition.
White matter forms the bulk of the deeper parts of the brain. It consists of glial
cells and myelinated axons that connect the various grey matter areas.
Cerebrum and cerebral cortex
 The procephalon is
divisible into diencephalon
and telencephalon
 The telencephalon is
divisible into a medial part
called the linea terminalis
 And two lateral part that
grows into cerebral
vesicles or telencephalic
vesicles
 These later forms the
cerebral hemispheres
 The cavities of the cerebral
vesicles forms the (lateral
ventricle) and that of the
diencephalon forms the
third ventricle
 Communicates through the
 Interventricular foramen
Cerebrum and cerebral cortex
Development of the cerebral vesicles/lobes
 DEVELOPMENT OF CHORIOD FISSURE/ PLEXUS/
TELACHOROIDEA

 With enlargement of the cerebral vesicles,their medial walls

apposed each other
 Along side,the corpus callosum is formed
 A groove bounded by the two medial surface is formed
 The floor of the groove forms the roof of the 3rd ventricle
 The medial wall is invaginated into the cavity of the lateral
ventricle
 The cavity of invagination forms the choriod fissure
 A fold of pia mater extends into this fissure and forms the
telachoroidea
 A bunch of capillaries iS formed within the telachoroidea
known as choriod plexus
DEVELOPMENT OF CHORIOD FISSURE/ PLEXUS
Cerebral cortex /Corpus stratum
 The cerebral or telencepalic vesicles wall has the usual
mantle and marginal walls
 Some of the cells of the mantle layer of the basal part
migrate into the marginal layer and form the cerebral cortex
 Others that do not migrate forms the corpus straitum
 Corpus straitum is one of the components of the basal
ganglia
 Which are groups of subcortical nuclei deep in the cerebral
hemispheres
 The largest component of the basal ganglia is the corpus
striatum which contains THE CAUDATE AND LENTICULAR
NUCLEI (THE PUTAMEN, GLOBUS PALLIDUS EXTERNUS,
AND INTERNUS), THE SUBTHALAMIC NUCLEUS (STN),
AND THE SUBSTANTIA NIGRA (SN).
Derivatives of the diencephalon
 Thalamus
 Epithalamus
 Hypothamus

We also look at other special sences such as the tongue,

nose
Then the embryology of the AUTONOMIC NERVOUS
SYSTEM
PRESENTATIONS
 Cerebral commissures and division of the cerebral cortex from

a developmental point of view(hippocampal, pyriform,

neocortex)

Embryology of the external ear

Embryology of the middle ear

Embryology of the inner ear

Glands connected with the nervous system(Hypophysis cerebri,

Pineal and adrenal gland)/ special sences(salivary gland)

DIENCEPHALON
 Most literatures explains it this way:
 After the establishment of the telencephalon,
 The lateral wall of the diencephalon becomes thickened
 Then is subdivided into three regions by the appearance of
two grooves called epithalamic and hypothalamic sulci.
 The central part lying between the two sides enlarges to
form the thalamus
 The part above the epithalamic sulci forms the epithalamus
 It is represented by the habenular nuclei and pineal body
 The part below the hypothalamic sulcus forms the
hypothalamus
 Various nuclei of the different component of the
diencephalon are formed as a result of multiplication of cells
in the mantle layer of the wall of the diencephalon
Cont.
 The endodermal wall of the foregut is seperated
from the surface ectoderm by a layer of mesoderm
 Soon the mesoderm are arranged like six bars that
run dorsol ventrally in the side wall of the foregut
Each of these bars grows ventrally in the floor of the
developing pharynx
It fuses with the corresponding bar of the oposite
side to form a pharyngeal or brachial arch
In the interval between two adjoining arches, the
endoderm extends outward in the form of a pouch
Opposite each pouch the surface ectoderm dips
inwards as an ectodermal cleft
l
Embryology of the tongue
 The tongue develops in relation to
pharyngeal arches in the floor of
developing mouth.
 Each arch arises as a
mesodermal thickning in the
lateral wall of the forgut
 Grows ventrally to become
continous with the corresponding
arch of the opposite side.
 The medial most part of the
mandibular arch proliferate to
form two lingual swellings.
 The lingual swellings are partially
seperated by a midline swelling
called the tuberculum impar
Embryology of the tongue
 immediately behind the tuberculum impar,
The epithelium proliferates to form a
downgrowth known as the thyroglossal duct
fom which the thyriod gland develops

This site is marked by a depression called

the foramen caecum

Another midline swelling is seen in relation

to the medial ends of the 2nd-4t h arch
(hypobronchial eminence)
This eminence is divided into cranial
part(2nd-3rd arch) copula
And a caudal part that forms the epiglotis

During the formation of pos.1/3rd of the

tongue, the 2nd arch mesoderm gets buried
below the surface

That of 3rd arch fuses with the 1st arch

Therefore the posterior 1/3rd formed by the

3rd arch mesoderm

The posterior most part is formed by the 4th

arch

The anterior 2/3rd formed by the fusion of

the tuberculum impar and two lingual
swellings
Embryology of tonsils
 The palatine tonsil develops
in relation to the lateral part
of the 2 pharyngeal pouch.
nd

 The endoderm lining the

pouch undergoes
proliferation
 Resulting in obliteration of
the pouch
 Lymphocytes collect in
relation to endodermal cells
 Aggregation of lymphiod
tissue give rise to TUBAL,
LINGUAL AND
PHARYNGEAL TONSILS
Eye embryology
Embryology of the eye
Eye embryology

STAGES IN DEVELOPMENT OF THE EYE
 Most literatures explains it as optic groove forms optic
sulcus
 Dividing into a distal part optic vesicle
 Proximal part optic stalk
 All surounded by surface ectoderm
 This optic vesicle grows laterally and forms
Lens placode
By coming in contact with the
Surface ectoderm
 STAGES IN DEVELOPMENT OF THE EYE
 The lens placode thickenes further to form the lens
vesicles
The lens vesicle detaches from the surface ectoderm
and invaginates into the optic vesicle
Due to this invagination, the optic vesicle becomes the
optic cup
Lens vesicle detaches from surface ectoderm to form
the lens which is not totally covered and it forms the
choriodal fissure
 STAGES IN DEVELOPMENT OF THE EYE
 The developing neural tube is covered by mesenchyme
 This extends to the developing optic cup
 Mesenchyme has an outer fibrous layer and an inner
vascular layer
 The outer forms the dura mater while the inner forms
the pia-arachniod mater
STAGES IN DEVELOPMENT OF THE EYE
Derivatives
 anterior outer fibrous layer of mesenchyme and
surface ectoderm-cornea
The cornea is made up of (the epithelium, Bowman's
layer, the stroma, Descemet's membrane, and the
endothelium.)
The epithelium is formed from the surface ectoderm

Posteriorly outer fibrous layer forms the sclera and the

extraocular muscles
STAGES IN DEVELOPMENT OF THE EYE
 the inner vascular layer forms the choriod and ciliary
body

Retina( outer pigmented/neural layer)

The outer pigmented is formed by the outer wall of the
optic cup and most of these cells are pigmented
The neural layer is formed from the inner wall of the
optic cup
The neural layer
 Matrix layer-Rods and cons
 Mantle layer-bipolar cells, ganglionic cells, supporting
tissue
 Marginal
 STAGES IN DEVELOPMENT OF THE EYE
 the vascular mesenchyme forms the iris but the
epithelium is formed from the optic cup
The eyelids and conjuctiva are derived from the surface
ectoderm
Formation of the lens
Anomalies
 ANOPHTHALMIA
 MICROPHTHALMIA
 COLOBOMA
 ANIRIDIA
 OPTIC NERVE HYPOPLASIA
 CONGENITAL CATARACTS
 CORNEAL OPACITY
 CONGENITAL GLAUCOMA.
EMBRYOLOGY OF THE SKIN
EMBRYOLOGY OF THE SKIN
Tissue organization of the skin (integumentum) :
- Epidermis — stratified epithelium on the outer surface
- Dermis — fibrous tissue beneath the epidermis
- Subcutaneous layer — loose connective tissue
beneath the two layers, compose mostly of fatty
tissues.
Cont
Germ layer of origin :
1. Epidermis — specializes from surface ectoderm not
involved in developing nervous system.
2. Dermis — differenciate from mesenchymal cells of
mesodermal somites (dermatomes).

Epidermis
Embryonic ectoderm originally a single sheet of cuboidal
cells.
Develop to become 2 layers in the 5th week :
1. periderm — flatten cells in outer side (surface).
2. cuboidal basal cells — reproductive cells → give rise
to new layers (periderm) above them.

During 3 – 4 months epidermis consist of 3 cell layers :

1. periderm
2. intermediary stratum
3. cuboidal basal cells
Cont
After the 4th months the epidermis becomes stratified
epithelia → consist multiple layers of cells :
1. Stratum germinativum — basal cells and their
immediate descendants next above.
2. Stratum granulosum — layer of cells next above
stratum germinativum → consist cells containing
keratohyalin granules.
3. Stratum lucidum — next above str. granulosum → thin
& clear cells containing degenerative keratohyalin.
4. Stratum corneum — flat cells on the surface → cell
cytoplasm undergo cornification to become cornified
dead cells with degenerate nuclei.

The cornification is not intensive in some areas : red

layer of lips & anus.
Keratohyalin is a protein structure found in cytoplasmic granules of
the keratinocytes in the stratum granulosum of the epidermis.
Cont
Cont
Development of melanocytes
Melanoblast → derived from neural crest − migrate to
dermis & penetrate epidermis in the 3rd month.

Melanoblast differenciate to form pigment granules

(melanosomes) → to become melanocytes.

The pigmentation intensity varies among races although

the number of melanocytes is not significantly different
from race to race.

The pigmentation is dependant on the activity of

tyrosinase → convert tyrosine to melanin
Cont
Langerhans cells − morphologically indistinguishable
from keratinocytes (epidermal cells); however they are
recognized by histochemical methods :
- they have membrane bound ATPase
- they have specific surface antigen different from
epidermal cells.

Derived from precursor cells in bone marrow.

Migrate to epidermis and function as antigen presenting
cells that process antigen entering epidermis.

The antigen is fragmented and presented it to

T-lymphocytes → mediate cellular immune response to
antigen
cont
Dermis
1. Skin component underneath the epidermis − compose
of
fibrous connective tissues.

2. Develop from lateral wall of somites (left & right) →

dermatomes.

3. The mesenchyme of dermatomes form collagen fibers

and elastin fibers during the 4 – 6 months of pregnancy.

4. The deepest layer of dermis − subcutaneous layer →

loose & fatty connective tissues; contain capillary blood
vessels & sensory nerve endings.

In some places the epidermis undergo modifications and

develop into skin glands and hairs.
Cont
 Anomalies & genetic diseases of the skin
1. Congenital failure of normal differentiation → skin
retain its fetal character.
- failure of pigment production/deposition in the
epidermis → albinism.
- over abundant of pigment production → melanism.
- atypical pigmentation give pigmented spot (mole).
- rough scaly skin due to abnormal cornification of
superficial layers → ichthyosis show thick plates
of epidermis.
2. Acquired disease/abnormality.
Xeroderma pigmentosum (xp)
 hypersensitivity to UV light & high incidence of UV induce skin
cancer.
Mutation leads to lack of enzyme necessary for excision repair
of DNA.

 UV light characteristically cause thymine dimers →

the dimer should be excised by exonuclease →
leaving a portion of damaged DNA.
Embryology of the nasal cavity
 Shortly after the anterior neuropore closes in the late third
to early fourth week
 the forebrain enlarges and pushes the overlying ectoderm
forward and laterally, creating the frontonasal process
 The enlarging brain and frontonasal process contribute to
an ectodermally covered invagination, the STOMODEUM,
which develops below them in the early fourth week.
 The ectoderm over the stomodeum comes to abut the
endoderm of the developing foregut to form the
oropharyngeal membrane.
cavity
 The sensory placodes arise from a common “preplacodal
field” at the anterior neural crest border
 By the end of the fourth week, the nasal placodes (or
olfactory placodes) develop as well-defined epiblastic
thickenings of 2–3 cell layers on either side of the
frontonasal process
 As each nasal placode starts to sink below the surface
as a nasal groove, first the lateral nasal process develops
in the early fifth week; then the medial nasal process
develops shortly thereafter.
As the medial and lateral nasal processes develop and
become more prominent, the nasal grooves deepen and
become the nasal pits.
The nasal pits is in open communication with the
stomatodeum
Embryology of the nasal cavity
Embryology of the nasal cavity
 An invagination of nasal pits form nasal sac
 The nasal sac expand dorsally and ventrally
 Dorsally is seperated from the stomatodeum by the
bucconasal membrane
 Ventrally it forms the anterior nares which forms the
nasal cavity
 Dorsally it forms the posterior nares
 The medial and lateral nasal process fuse to form a
partition between the nasal pits and stomatodeum
 Partition is called primitive palate
 The posterior nares breaks from the bucconasal
membrane
Cont
AUTONOMIC NERVOUS SYSTEM
SYMPATHETIC NEURONS
Any sympathetic pathway consist of two neurons
1. A preganglionic
2. Postganglionic neuron
 The preganglionic neurons develop in the mantle layer of
thoracolumbar region of the spinal cord(T1 –L2-L3)
 The postganglionic neurons are derived from cells of the
neural crest
PARASYMPATHETIC NEURONS
The neurons are formed in two distinct situations
1. Some neurons are formed in the mantle layer of the sacral
part of the spinal cord
2. Some of them are formed in relation to the general
visceral efferent nuclear column of the brain stem
Goodluck