The DEVELOPMENT of the
NERVOUS SYSTEM
Joselito B. Diaz, MD, FPNA
COLLEGE OF REHABILITATION SCIENCES
Origin of the Nervous System
• At day 16 after
conception, the
embryo consists of
three germ layers
– Ectoderm
– Mesoderm
– Endoderm
Neural Plate
• 3rd week of
development, in the
dorsum of the embryo, a
pear-shaped ectodermal
plate rostral to the
primitive knot
developed
• The nervous system
developed from the
neural plate
Neural Plate
• Notochord and
paraxial
mesoderm
induce the
overlying
ectoderm to
differentiate into
the neural plate
Primary Neurulation
• Rapid cell
proliferation at the
margins of the
neural plate
• Neural groove
forms between the
neural folds
Primary Neurulation
• Neural folds grow
towards each other
to form the neural
tube
• On the 22nd day,
fusion begins at the
level of the future
lower medulla
• Closure proceeds in
cranial and caudal
directions
Primary Neurulation
• Rostral neuropore closes
at the 25th day of
gestation
• Caudal neuropore closes
at the 27th day of
gestation
• Rostral 2/3 – brain
• Caudal 1/3 – spinal cord
up to the lumbar area
Neural Crest
• Cells from the lateral margin
of the deepening neural
groove
• Not incorporated in the
neural tube but forms
temporarily a strip of
ectodermal cells between
the neural tube and the
overlying ectoderm
• Migrates to the dorsolateral
aspect of the neural tube
Neural Crest
• The neural crest cells give
rise to the following
structures
– Dorsal root ganglia
– Sensory ganglia of cranial
nerves (CN V, VII, IX, X)
– Autonomic ganglia
– Chromaffin cells of the
adrenal medulla
– Schwann cells
– Melanocytes
– Arachnoid and pia mater
– Mesenchyme of the branchial
arches
Secondary Neurulation
• Caudal neural tube
formation i.e. sacral and
coccygeal segments
• Begins at 28th to 32nd day
of gestation
• Caudal eminence enlarges
and cavitates
• Attach to neural tube and
cavity becomes
continuous
Neural Tube Defects
• Result in various errors of neural tube closure
• Accompanied by alterations of axial skeleton as
well as of overlying meningovascular and dermal
covering
• Congenital malformations associated with
defective primary neurulation are called dysraphic
defects
• Most dysraphic defects occur at the level of the
anterior or posterior neuropore
Neural Tube Defects
• Dysaphic defects in order of decreasing severity
–
–
–
–
–
Craniorachischisis totalis
Anencephaly
Rachischisis
Encephalocele
Spina bifida
• Congenital abnormalities associated with
defective secondary neurulation are known as
myelodysplasia
Craniorachischisis Totalis
Anencephaly
Rachischisis
Encephalocele
Encephalocele
Spina Bifida
Spina Bifida
Spina bifida occulta
Meningocele
Myelomeningocele
Tethered Cord
3 Primary Brain Vesicles
• Following closure of the
anterior neuropore,
rapid growth of neural
tissue in the cranial
region
• On the 4th week of
development, the
cephalic end shows 3
dilatations, the primary
brain vesicles, and 2
flexures
Primary Brain
Vesicles
• 3 primary brain vesicles
– Prosencephalon (forebrain)
– Mesencephalon (midbrain)
– Rhombencephalon (hindbrain)
• The caudal portion of the
neural tube forms the spinal
cord
• The 3 part brain begins to
assume a “C”-shape by the
formation of the cephalic
flexure at the level of the
mesencephalon and the
cervical flexure between the
hindbrain and spinal cord
5 Secondary Brain Vesicles
• On the 5th week of
development, the 3 part brain
begins to develop 5 vesicles
• The prosencephalon subdivides
into two parts: telencephalon
and diencephalon
• At the cephalic flexure, the
mesencephalon remains tubular
and undivided
• The rhombencephalon
subdivides into two parts:
metencephalon and
myelencephalon
Secondary Brain Vesicles
• The mesencephalon is
separated from the
rhombencephalon by a
deep furrow, the
rhombencephalic
isthmus
• The pontine flexure
separates the
metencephalon and
myelencephalon
Primary Division of the Developing Brain
Primary
vesicle
Primary division
Subdivision
Adult structures
Telencephalon
(lateral
ventricles)
Cerebral cortex, subcortical
white matter, amygdala, basal
ganglia, hippocampus,
olfactory bulb and tract
Diencephalon
(third ventricle)
Thalamus, hypothalamus,
epithalamus, subthalamus,
optic nerve and retina
Forebrain
vesicle
Prosencephalon
Midbrain
vesicle
Mesencephalon
(cerebral aqueduct) Mesencephalon
Hindbrain
vesicle
Rhombencephalon
(fourth ventricle)
Midbrain
Metencephalon
Pons, cerebellum
Myelencephalon
Medulla oblongata
Development of the
Spinal Cord
Neuroepithelium
• After closure, cells
of the original
single layered
tube divide to
form a
pseudostratified
neuroepithelium
• Also known as
matrix cells
Neuronal Proliferation
• Stem cells in the
periphery replicate
their DNA then migrate
towards the cavity of
the tube and divide;
the two daughter cells
then migrate back to
the periphery
• “to and fro migration”
• Rate can be
250,000/min
First Wave of Proliferation
• In the earliest phase,
stem cells divide
symmetrically to
produce two additional
stem cells
• Later phase,
asymmetrical division –
1 stem cell and 1 postmitotic neuronal cell
(neuroblast)
Intermediate or
mantle zone
Ventricular or
germinal zone
Second Wave of Proliferation
• “Switch point”
• Stem cells stopped
making neuroblasts
and produces
glioblasts
• The ventricular layer
differentiates into the
ependymal lining of
the ventricles and
central canal
Neuroblasts and Glioblasts
• Neuroblasts give rise to nerve fibers that grows
peripherally and form a layer external to the mantle
zone called the marginal zone
• Mantle zone will form the gray matter while the
marginal zone will form the white matter of the spinal
cord
Spinal Cord Development
• As the spinal cord develops,
neuroblasts in the mantle layer
proliferate in 2 zones
• In cross section the mantle layer
develops a characteristic
“butterfly”-shape of gray matter
• The lateral walls of the tube
thicken but leave a shallow,
longitudinal groove called the
sulcus limitans which separates
the developing gray matter
– Dorsal alar plate
– Ventral basal plate
Spinal Cord Development
• The neuroblasts in the basal plate will give rise to the motor
neurons of the of the anterior horn
• The neuroblasts in the alar plate will become the sensory
neurons of the posterior horn
• The lumen of the spinal cord becomes the central canal
• Anterior median fissure and posterior median septum
Anterior (Ventral) Motor Roots
of the Spinal Nerves
• The medial group of
motor neurons form large
multipolar cells whose
axons supply the
musculature of the body
• The lateral group of
motor neurons give rise to
autonomic preganglionic
fibers (intermediolateral
cell column)
– T1-L2: sympathetic outflow
– S2-S4: parasympathetic
outflow
Posterior (Dorsal) Sensory Roots
of the Spinal Nerves
• The first neurons of the
sensory pathway are
derived from the neural
crest cells
• Each neuroblast (Dorsal
root ganglion cell)
develops 2 processes
• The central processes
enter the spinal cord
• The peripheral processes
join the motor axons and
becomes the spinal nerve
The Sectional Organization of the Spinal Cord
Positional Changes of the Cord
• In the first 2 months of
development, the spinal
cord extends the entire
length of the vertebral
column and the spinal
nerves pass through the
intervertebral foramina at
their level of origin
Positional Changes of the Cord
• With increasing age, the
vertebral column lengthen
more rapidly than the spinal
cord
• At birth, the terminal end of
the spinal cord lies at the level
of the 3rd lumbar vertebra
• The anterior and posterior
roots of the spinal nerves
below L1 descend within the
vertebral canal until they reach
their appropriate exits through
the intervertebral foramina
Positional Changes of the Cord
• Filum terminale: the
slender fibrous strand of
pia mater which attach
the coccygeal cord to
the coccyx
• Cauda equina:
collectively, the anterior
and posterior roots of
the spinal nerves below
L1 and the filum
terminale
Development of the Brain
Development of the Brain
• Neuroblasts of the brainstem develop in a manner similar
to the spinal cord
• From the medulla through the midbrain, alar and basal
plates form motor and sensory columns of cells that
supply cranial nerves
• However, the organization of alar and basal plates differ
from of the spinal cord in that
– 1) in the medulla and pons, the alar plate lies lateral to the basal
plate, not dorsal to it, since the 4th ventricle is “open”
– 2) there are migrations of neuroblasts of both plates from the
ventricular floor to other locations
• The diencephalon and cerebral hemispheres develop from
the alar plate
• The cerebellum also develops from the alar plate
Medulla
• The expansion of fourth ventricle moved the
alar plates laterally
• The neuroblasts at the basal plates form the
motor nuclei of the CN IX, X, XI and XII
• The neuroblasts of the alar plates form the
sensory nuclei of the CN V, VIII, IX and X,
the gracile and cuneate nuclei and the olivary
nuclei
Medulla
(Myelencephalon)
• The roof plate of the myelencephalon consists of
a single layer of ependymal cells covered by a
vascular mesenchyme, the pia mater
• The two combined are known as the tela
choroidea
• Vascular tufts of tela choroidea project into the
cavity of the fourth ventricle to form the choroid
plexus, which produces the cerebrospinal fluid
Medulla
(Myelencephalon)
• Local resorptions of the roof plate occur at
the 4th and 5th month of development
• Lateral foramina of Luschka and median
foramen of Magendie
• Escape of cerebrospinal fluid from the
ventricles into the subarachnoid space
Pons
(Metencephalon)
• The pons arises from the anterior part of the
metencephalon but also receives cellular contributions
form the alar plate of the myelencephalon
• The neuroblasts of the basal plate form the motor nuclei
of the CN V, VI and VII
• The neuroblasts of the alar plate form the sensory nuclei
of the CN V, VII, VIII and the pontine nuclei
• The axons of the pontine nuclei grow transversely to
enter the developing cerebellum
Cerebellum (metencephalon)
• Formed from the posterior part
of the alar plates of the
metencephalon
• On the 5th-6th week of
development, the rhombic lips
project caudally over the roof
plate of the fourth ventricle
and unite with each other in
the midline to form the
cerebellar plate
• By the 12th week, the plate
shows the small midline vermis
and two lateral hemispheres
Cerebellum
• The neuroblasts from the
ventricular zone migrates
toward the surface of the
cerebellum to form the
cerebellar cortex
• Other neuroblasts remain
close to the ventricular zone
and differentiate into the
cerebellar nuclei (dentate,
emboliform, globose and
fastigial nuclei)
Midbrain
(mesencephalon)
• The midbrain is the least
modified of the brainstem
structures with regard to basal
and alar plates
• Neuroblasts of alar plates migrate
to form the inferior and superior
colliculi and the mesencephalic
nucleus of CN V
• Neuroblasts in the basal plates
will form the motor nuclei of CN
III and IV
• The embryologic origin of the
red nucleus and substantia nigra
(from alar or basal plates) are
uncertain
• The cavity of the original neural
tube is little modified in the adult
midbrain except to be narrowed
by growth of the surrounding
midbrain structures; it remains as
the narrow cerebral aqueduct
Diencephalon
• The diencephalon develops from the median portion of
the prosencephalon and consists of a roof plate and
two alar plates but lacks the floor and basal plates
• The most caudal part of the roof plate develops into
the pineal body or epiphysis
• The tela choroidea gives rise to the choroid plexus of
the third ventricle
Diencephalon
• The alar plates form the lateral walls of the diencephalon
• The hypothalamic sulcus divides the plate into a dorsal
thalamus and a ventral hypothalamus
• With continued growth of the thalami, the third ventricle
becomes narrowed and the two thalami may fuse
forming the interthalamic connection or massa
intermedia
Telencephalon
• The telencephalon consists of
two lateral outpocketings, the
cerebral hemispheres and a
median portion, the lamina
terminalis
• The lateral ventricles
communicate with the third
ventricle through the
interventricular foramina of
Monro
Cerebral Hemisphere
• Each cerebral hemispheres
arise at the beginning of the
5th week of development
• At the basal part of the
hemispheres, the corpus
striatum arises
– Dorsomedial portion, the
caudate nucleus
– Ventrolateral portion, the
lentiform or lenticular nucleus
(putamen and globus
pallidus)
Cerebral hemispheres
• The mesenchyme between the cerebral hemispheres
condenses to form the falx cerebri
• The cerebral hemispheres continue to grow and expand,
first anteriorly to form the frontal lobes, then laterally and
superiorly to form the parietal lobes and finally posteriorly
and inferiorly to produce the occipital and temporal lobes
• The cortex covering the lentiform nucleus, the insula, lags
in growth and later overgrown by the adjacent temporal,
frontal and parietal lobes
Cerebral Hemispheres
• Ascending and descending tracts of the
cerebral hemispheres pass between the
thalamus and caudate nucleus medially and
lentiform nucleus laterally
• Collectively known as the internal capsule
Cerebral
Cortex
• The neuroblasts from the ventricular zone
migrates toward the surface of the cerebral
hemispheres to form the cerebral cortex
• At the final part of fetal life, the surface of the
cerebral hemispheres grows so rapidly that many
gyri separated by fissures or sulci appear on its
surface
Schizencephaly
Lissencephaly
Polymicrogyria
Commissures
• The lamina terminalis forms a bridge between the two
hemispheres and enables nerve fibers to pass from one cerebral
hemisphere to the other
• Anterior commissure: connects the olfactory bulb and the two
temporal lobes
• Fornix: connects the hippocampus in each hemispheres
• Corpus callosum: massive connection between hemispheres
• Optic chiasm: contains fibers from the medial halves of the
retinae
Myelination in the Central Nervous System
• Formed by the oligodendroglia
• At 4th month of development,
myelination begins in the sensory
fibers in the cervical spinal cord and
then extends caudally
• Myelination in the brain begins at the
6th month but is restricted to the
basal ganglia
• At birth, the brain is largely
unmyelinated
• Myelination is not haphazard but
systematic, occurring in different
nerve fibers at specific times
• Myelination within the CNS
progresses most rapidly after birth
and continues up to adult life
The DEVELOPMENT of the
NERVOUS SYSTEM
Joselito B. Diaz, MD, FPNA
COLLEGE OF REHABILITATION SCIENCES