Neuroscience 1a – Development of the Nervous System
Anil Chopra
1. Review the development of the neural tube from the neurectoderm, and give an
example of a clinical condition which results from abnormal development.
2. Explain what is meant by the neural crest cells, and give examples of their
developmental fates.
3. Briefly describe how a simple tubular structure (the early neural tube) can give
rise to the shape of the mature brain through differential growth and flexures.
4. Outline the cellular basis of formation of the ependymal, grey matter (mantle
layer) and white matter (marginal layer) regions of the spinal cord, and the
separation of the grey matter into sensory (alar) and motor (basal) regions.
5. Briefly outline how the development of the brainstem diverges from that of the
spinal cord.
6. Briefly outline how cortical layers form from the neuroepithelium.
Early Development
A) Trilaminar stage – 3 layers
a. Ectoderm thickens up in midline and
becomes neural plate
b. These fold to become neural folds
c. Fuse to become neural tube.  CNS
B) Neural Crest  PNS
a. Separates off and moves laterally.
Neuroepithelium of Neural Tube
- forms the cells of the CNS
 Neuroblasts
o Develop into neurones with cell bodies in the
CNS.
 Glioblast
o Give rise to glial cells (astrocytes,
oligodendrocytes)
o NB. Microglia develop from the mesoderm as
they are blood cells that develop
 Ependymal Cells
o Single layers of lining cells
Neural Crest Cells
- cells found at the tips of the ridges of the neural groove
and are isolated in neurulation. They migrate during
development to form:
 Sensory neurones of dorsal root ganglia and cranial
ganglia
 Postganglionic autonomic neurones (e.g.
sympathetic chain).
 Schwann cells of Peripheral Nervous system.
 Non-neuronal derivatives e.g. melanocytes
Cellular Process
Proliferation occurs at the walls of the neural tube. This involves several repeats of
the cell cycle.
Outside
Inside
Differentiation occurs on the outer surface of the CNS. They become neuroblasts and
glial cells.
 The neural tube surrounds the neural canal which in turn forms the canal of the
fully developed spinal cord
 Neuroblasts are contained within the tube
 The neuroblasts adjacent to the canal in the Ependymal layer divide and migrate
outwards within the tube forming the mantle layer, where they differentiate into
neurones and form the grey mater of the cord
 These cells then send fibres/developing processes out peripherally forming the
white layer of the cord = marginal layer
 The neuroblasts in the primitive grey matter form 2 discrete populations – the alar
and basal plates separated by a shallow groove called the sulcus limitans
o Alar Plate – forms the posterior dorsal sensory horns of the cord
o Basal Plate – forms the anterior ventral motor horns of the cord. It also
forms the parasympathetic and sympathetic pre-ganglionic neurons
 In the first 8 weeks the spinal cord and vertebral column are the same length.
After week 8 the vertebral column grows faster, so by week 40 the spinal cord
stops at L3, and by adult life L1
 The spinal cord is clothed in 3 layers of meninges similar to the brain, but with
certain differences:
 There is an extradural (epidural) space containing fat and a venous plexus
 The pia mater has lateral projections called dentate ligaments which extend to the
dura and help to stabilize the spinal cord
 The lower end of the spinal cord is anchored to the coccygeal vertebrae by a
strand pia mater (pial thread) called the filum terminale
 The subarachnoid space below the end of the spinal cord, the lumbar cistern (L1),
contains the lumbar & sacral spinal roots (nerve roots) is called the cauda equine
 The strand of the pia mater between the coccyx and lower end of the spinal cord =
fibrum terminale.
Neural Tube formation
 First signs of nervous system development occur in the third week of gestation
 Initial development is under the influence of secreted factors from the notochord
with the formation of the neural plate along the dorsal aspect of the embryo
 Fusion of neural groove to form the neural tube starts half-way along at the level
of the fourth somite and continues caudally and rostrally, with closure by 4th week
of gestation
 Rostral (head) end fused on day 25
 Caudal (tail) end fused on day 27
 Folding = neurulation
 Ectoderm of trilaminar disc → neural plate → folds to form neural groove →
neuroepithelium of neural tube and neural crest cells
 Abnormalities in process of closure:
 Ancephaly – at the anterior/rostral end → no cerebral vesicles form and so no
brain development
 Spina Bifida – at the posterior/caudal end → leads to defects in meninges and
neural tissue → herniation
Development of the Spinal Cord
Central canal
Ependymal layer
Grey matter
White matter
After more proliferation occurs…
Neurons here
are interneurons
(alar plate)
Neural crest
cells form
sensory
neurons in
dorsal root
ganglion
Neurons here
are
motoneurons
and
interneurons
(basal plate)
Spinal Cord Roots
 Spinal cord lies within the vertebral canal and extends from the foramen magnum
to the lower border of L1
 It is enlarged in two sites – cervical and lumbar regions, corresponding to
innervations of the upper and lower limbs
 It consists of a core of grey matter surrounded by white matter. The neuronal cell
bodies which make up the central grey mater are arranged in laminae (of Rexed).
The white matter comprises myelinated and non-myelinated axons with short
pathways that interconnect adjacent segments of the spinal cord and longer tracts
to and from the brain
 The posterior dorsal horns receive sensory input via spinal nerves and their
accompanying cell bodies in the dorsal root ganglia. This information is used in
spinal reflexes or is projected to the brain
 Motor and pre-ganglionic autonomic fibres exit via the anterior ventral root. The
motor cell bodies are found in the ventral horn of the spinal cord while the preganglionic cell bodies of the nervous system are found in the intermedio-lateral
column of the spinal cord
 In the thoracic and upper lumbar regions the intermediate horns contain
sympathetic pre-ganglionic motorneurons whose axons control visceral function
via the ventral roots and spinal nerves forming the intermediolateral column
Development of The Brain
The brain develops from the top (rostral) of the neural tube.
In the first 3 weeks it enlarges and forms, 3 Primary Vesicles
 Future forebrain
 Future midbrain
 Future hindbrain
Future forebrain
(prosencephalon)
Future midbrain
(mesencaphalon)
Future hindbrain
(rhombencephalon)
Future spinal cord
During the next week it develops into 5 vesicles
 Hind brain splits into 2 (pons & medulla).
 Forebrain splits into 2 separate parts (becomes the 2 cerebral hemispheres)
Fore
Diencephalon
Mid
Pons
Hind
Medulla
(approx 5 wk)
At 8 weeks
 Lateral ventricles form in forebrain
 Third ventricle in the middle
 Cerebellum outpouch from hindbrain.
Developing
hemisphere
LV
LV
Fore
III
aqueduct
Developing
cerebellum
(approx 8 wk)
IV
Mid
Hind
(4 wk)
Cephalic flexure
Pontine flexure
Cervical flexure
(5
wk)
(8
wk)
At 4 weeks, 2 flexures fold the neural tube
inwards.
At 8 weeks, folding becomes more and more exaggerated.
Folding of the tube creates 3 flexures:
st
nd
 Cephalic flexure – between 1 and 2 vesicles
nd
rd
 Pontine flexure – between 2 and 3 vesicles
rd
 Cervical Flexure – between 3 vesicles and spinal cord
Development of the Brainstem
The arrangement of the brainstem is similar to that of the spinal cord. Exceptions to
note are:
 Neurones are clustered together into nuclei.
 Fourth ventricle runs in the middle, disrupting the pattern of grey matter.
 Neurones with motor function lie medial and ventral.
 Neurones with sensory function lie lateral and dorsal
 Nuclei with autonomic functions lie in between these.
Development of the Cortex
Cortex of the cerebral
hemispheres and cerebellum is
formed from the migration of
neuroblasts formed from the
neuroepithelium toward the
surface of the pia. This pattern is
different for the different
structures.
Developmental Disorders of the NS.

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
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All the development has to occur at the right time.
It is controlled by a mixture of genetic programming and the environment.
It occurs early in gestation.
It involves various different complicated processes including proliferation,
differentiation, migrastion, synapse formation.
Genetic mutation and environmental factors such as dietary insufficiencies and
teratogens may interfere with the processes.
Research: - replace lost neurones by regulation of stem cell differentiation
- axon guidance can be used in inducing CNS regeneration.