SYSTEMIC EMBRYOLOGY

ANA 331
Development Of Central Nervous System And
Spinal Cord

Auza, M I (BSc, MSc)

Department of Human Anatomy

Faculty of Basic Medical Sciences
Bingham University, Karu
 WISDOM QUOTE
“Until you are willing
to change your
approach, you cannot
improve on your
result”
 Introduction
• Following fertilization, the nervous system begins to
form in the 3rd week of development.
• It continues after birth and for many year into the
future.
• Structurally the nervous system is divided into two
parts:
• Central nervous system: consisting of the brain and the
spinal cord.
• Peripheral nervous system: consists of cranial and
spinal nerves, ganglia, plexuses, and sensory receptors.
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 Early Stages
• At the end of week two,
1. A structure called the primitive
streak appears in the epiblast layer
of the bilaminar disk.
• The primitive streak is a groove in
the midline of the epiblast which
appears during the third week.
• Within the primitive streak lies a
primitive node at the cranial end,
and
• Within the primitive node lies the
primitive pit.

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 Formation of Primitive Pit and
Primitive node
• The formation of primitive steak firmly establishes the
cranial/caudal axis.
• At the cranial end of the primitive streak, epiblast cells
ingress at a greater rate forming a circular cavity known as the
primitive pit.
• The movement of epiblastic mesenchymal cells down primitive
streak is known as ingression
• As the primitive streak and pit elongate, migrating epiblast cells
join the streak at the cranial end, forming a mass of cells called
the primitive node, which becomes the primary tissue organizer
where transcription factors and chemical signaling drive
induction of tissue formation.
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 Formation of three Germ layer
• Cells within the epiblast
migrate downward through
the primitive streak, giving
rise to three layers from
the initial two (Epiblast
and Hypoblast)

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 Formation of three
Germ layer
These three germinal
layers form the
trilaminar embryonic
disk:
Endoderm – innermost layer
Mesoderm – middle layer
Ectoderm – outermost layer

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 Formation of three Germ layer:
Endoderm
• The first set of cells to
move down primitive
streak integrate into
the hypoblast layer and
transform into
endoderm, the first of
the three germ layers.

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 Formation of three Germ
layer: Mesoderm
• The second set of cells to
detach and ingress will fill
in the space between the
endoderm and epiblast layer
to form the second germ
layer termed mesoderm.

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 Formation of three Germ layer:
Endoderm
• Finally, the remaining
epiblast cells will
transform into the
final germ layer,
ectoderm.

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 Formation of three Germ layer
• These three cell layers
(ectoderm, mesoderm and
endoderm) are then
responsible for forming the
different tissues of the
fetus.
• The nervous system is
derived from the ectoderm,
which is the outermost layer
of the embryonic disc and it
begins with the process
called Neurulation.

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 Neurulation
• Neurulation: Refers to the formation and closure of the
neural tube.
• It is the transformation of the neural plate into
the neural tube.
• The embryo at this stage is termed the neurula
• The process begins when the notochord induces the
formation of the central nervous system (CNS) by
signaling the ectoderm germ layer above it to form the
thick and flat neural plate.
• The neural plate folds in upon itself to form the neural
tube, which will later differentiate into the spinal
cord and the brain, eventually forming the central
nervous system 12
 Neurulation
• In the third week (16th day)
of development,
the notochord appears in the
mesoderm.
• The notochord secretes
growth factors
which stimulate or induces
the overlying ectoderm to
differentiate into
neuroectoderm forming a
thickened structure known as
the neural plate.
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 Neurulation
•The lateral edges
of the neural
plate then rise to
form neural
folds.

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 Neurulation
• The neural folds move
towards each other and
meet in the midline,
fusing to form the neural
tube that loses its
connection with the
surface ectoderm.
• Neural tube is precursor
to the brain and spinal
cord.
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Genesis of nervous system and special sense organs.
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 Neurulation Cont’d
• Once the Neural tube is formed it
opens at both ends at the anterior or
rostral and posterior neuropores.
• The anterior and posterior neuropores
connect the lumen of the neural tube
with the amniotic cavity.
• The anterior neuropore closes during
week 4 (day 25) and becomes the
lamina terminalis
• Failure of the anterior neuropore or
lamina terminalis to close results in
upper (Neural tube defects) NTDs;
(e.g., anencephaly). 17
 Neurulation Cont’d
• The posterior neuropore closes during week 4 (day 27).
• Failure of the posterior neuropore to close results in
lower (Neural tube defect) NTDs (e.g., spina bifida).
• The rostral part of the neural tube becomes the adult
brain.
• The caudal part of the neural tube becomes the adult
spinal cord.
• The lumen of the neural tube gives rise to the
ventricular system of the brain and central canal of
the spinal cord.
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 Clinical Correlation: Defects in
Neural Tube Formation
Anencephaly (Craniorachischisis) Characteristic features
• A congenital anomaly that results • Vault of skull is absent.
from failure of the neural tube • Brain is represented by a mass of
to close at the cephalic end, degenerated tissue exposed to the
leading to the partial absence surface.
of the brain and skull. • Cord is open in the cervical region.
• Associated defective • Appearance of child is characteristic
development of the vault of the with prominent eyes bulging forward,
skull produces anencephaly and chin continuous with chest due to
• A physician can detect this absence of neck.
anomaly:
(a) by ultrasonography in later part
of pregnancy or
(b) by detecting the α-fetoprotein
level of amniotic fluid after
transabdominal amniocentesis. N.B. The level of α-fetoprotein is raised in anencephaly
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 Clinical Correlation: Defects in
Neural Tube Formation
Spina Bifida (Rachischisis) Characteristic features
• A congenital anomaly that results • Failure of dorsal portions of the
from an incomplete closure of vertebral arches to fuse with
the neural tube at the caudal end each other.
(caudal neuropore). • Usually localized in the
lumbosacral region.
• Defective development of
associated vertebral arches • Neural tissue is widely exposed
to the surface.
cause Rachischisis.
• Occasionally the neural tissue
shows considerable overgrowth,
usually, however, the excess
tissue becomes necrotic shortly
before or after the birth.
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 Classification of Spina Bifida
• Depending upon herniation of structures present within the
spinal canal through the defect, it is classified into following
forms.
(a) Spina bifida occulta: No herniation of structures of spinal
canal through the gap. A tuft of hair is often present over the skin
at the site of defect.
(b) Meningocele: Meninges surrounding the spinal cord bulge out
through the defect in the vertebral arches, forming a cystic
swelling beneath the skin containing cerebrospinal fluid (CSF).
(c) Meningomyelocele: Spinal cord and spinal nerve roots also
herniate along with the meninges if the defect is large.
(d) Rachischisis: The neural tissue is exposed to surface. It is, in
fact, due to failure of fusion of caudal neuropore.

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 Congenital malformations due to
defective ossification of skull bones
• A gap in the skull caused by defective ossification
makes meninges surrounding the brain to bulge out
of the cranial cavity producing Meningocele.
• If defect is large, a part of brain tissue may also
herniate producing Meningoencephalocele.
• If herniated part of the brain contains a part of
ventricular cavity, it is termed
Meningohydroencephalocele.

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 Formation of Neural Crest
Cells
• As the neural folds come
together and fuse, cells at the
tips of neural folds break away
from the neurectoderm to form
the neural crest cells.
• The surface ectoderm of one
side becomes continuous with
the surface ectoderm of
opposite side over the neural
tube.

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 Neural Crest Cell
• Thus neural crest cells at the
tips of neural folds do not
participate in the neural tube
formation.
• The neural crest cells at first
remain in the midline between
the dorsal surface of the
neural tube and the surface
ectoderm, and
• Then neural crest cells forms
two-cell clusters
dorsolaterally, one on either
side of the neural tube.

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 Differentiation of neural crest cells
• The neural crest cells
differentiate to form
• Cells of dorsal root
ganglia
• Sensory ganglia of
cranial nerves
• Autonomic ganglia
• Adrenal medulla
• Chromaffin tissue
melanocytes, and
• Schwann cells.

Structures derived from neural crest25cells

 Formation of Ectodermal Placodes
• Prior to the neural tube closure, the neural fold contains two
types of cell populations:
• Neural crest cells
• Neuroepithelial cells.
• During neurulation, the neural crest cells are detached and
neuroepithelial cells get incorporated into the surface
ectoderm.
• These areas of neuroepithelium within the surface ectoderm
are termed ectodermal placodes

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Clinical Relevance: Defects in Neural
Crest Cells Formation
Neurocristopathy
• It is a term used to describe any disease
related to mal-development of neural crest
cells.
• Some neurocristopathies are indicated in the
following:
• Medullary carcinoma (MC) of thyroid
• Schwannoma
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 Development of the Spinal Cord
• The spinal cord develops from the neural tube.
• The cranial end of the neural tube forms the brain
and cerebellum
• The caudal end develops to form the spinal cord.
• Cells on the dorsal side form the alar plate, which
subsequently becomes the dorsal horn (posterior).
• Cells at the ventral end form the basal plate, which
then becomes the ventral horn (anterior).
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 Histogenesis of Neural Tube
• The neural tube increases in
thickness due to repeated
mitosis of its epithelial lining.
• By the middle of fifth week
of embryonic development, the
transverse section of recently
closed neural tube (according
to classical theory) reveals
three distinct layers or zones.
• From within outward these are
(a) matrix (ependymal) zone,
(b) mantle zone, and
(c) marginal zone.

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 Matrix, Mantle and Marginal zone
• The Matrix is thick and lines
the enclosed cavity
(neurocele).
• Its numerous cells
undergoing mitosis produce
neuroblasts and
spongioblasts;
• The former (neuroblasts)
develop into neurons and the
latter (spongioblasts)
develop into neuroglial cells.

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 Matrix, Mantle and Marginal zone
• The neuroblasts migrate to
the adjacent mantle zone,
the future gray matter of
the spinal cord and
• Their axons (neuroblast)
enter the external marginal
zone, the future white
matter.

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 Matrix, Mantle and Marginal zone
• Some central processes of
dorsal root ganglia ascend in
the marginal zone while
others synapse with neurons
in the mantle zone.
• Once histogenesis is
complete, the remaining
matrix cells differentiate
into ependymal cells lining
the central canal

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 Matrix, Mantle and Marginal zone
• As development proceeds, these neuroepithelial cells give rise to
another cell type called nerve cells or neuroblasts (cells having
round nuclei with dark staining nucleoli)
• The neuroblasts form a zone that surrounds the neuroepithelial
layer. It is known as mantle zone.
• Mantle zone later forms the gray matter of the spinal cord.
• The outermost layer of the spinal cord contains fibers
emerging from neuroblasts in the mantle layer and is known as
the marginal layer.
• Myelination of nerve fiber gives this layer a white appearance
and is referred as the white matter of the spinal cord.

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 Development of Functional Columns
• On cross section, the cavity of neural
tube appears like a vertical slit.
• Due to formation of vertical slit, the
dorsal and ventral walls of neural tube
remain thin and,
• The dorsal wall of neural tube is called
roof
• The ventral wall of neural tube is called
floor plates.
• The lateral walls of neural tube get
thickened.
• On each side, the lateral wall of
neural tube is demarcated into dorsal
and ventral regions by an inner
longitudinal sulcus called sulcus
limitans.
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 Development of Functional Columns
• The cells of dorsal region or
alar lamina are functionally
afferent/sensory while
• The cells of basal lamina are
efferent/motor.
• The axons of cells of basal
lamina leave the cord as
ventral roots and join with
peripheral processes of
dorsal root ganglia to form
spinal nerves.
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 Arrangement of Alar and Basal
laminae
• The cells of alar and basal laminae are arranged into
longitudinal columns.
• Each lamina reveals two columns.

ALAR LAMINAE BASAL LAMINAE

General somatic afferent column General visceral efferent column

General visceral afferent column General somatic efferent column

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 ALAR LAMINAE
• The two afferent columns of alar
lamina receive axons from dorsal
root ganglia.
General somatic afferent column:
• It extends throughout the spinal
cord and receives impulses from
superficial (cutaneous) and deep
(proprioceptive) receptors.
General visceral afferent column:
• It is confined to thoracolumbar
and sacral regions only and
receives impulses from viscera
and blood vessels

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 BASAL LAMINAE
• The two afferent columns of
basal lamina give rise to motor
fibres.
General visceral efferent column:
• It is confined to thoracolumbar
and sacral regions only and
provides preganglionic fibers
(synapsing in ganglia) to viscera,
glands, and blood vessels.
General somatic efferent column:
• It extends throughout the spinal
cord and provides fibers that
innervate skeletal muscles

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Positional Changes of the Spinal Cord.
• At week 8 lengths of spinal
cord and vertebral column
are equal.
• The spinal cord extends
along entire length of
vertebral canal and the
spinal nerves exit
intervertebral foramina at
the level of their origin.

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Positional Changes of the Spinal Cord.
• Due to differential growth of
the cord and vertebral
column, the intervertebral
foramina do not remain at the
level of the spinal nerves.
• In order to exit from
corresponding intervertebral
foramina due to recession of
the spinal cord, the spinal
nerves are forced to go down
in oblique direction.

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Positional Changes of the Spinal Cord
• At week 24, the lower end
of spinal cord ends at S1
vertebrae.
• At birth, the lower end of
spinal cord ends at the level
of L3 vertebra.
• In adults, due to further
recession of the cord, the
lower end of spinal cord
ends at the lower border of
L1 vertebra.

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