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What are the stages of CNS development

Blastogenesis, gastrulation, dorsal induction, ventral induction, neural proliferation, neuronal migration and then axonal myelination.



Days 1-13

Development from a fertilized embryo ito a bilaminar blastocyst implanted in the uterus with amniotic and yolk sacs



Gastrulation occurs from day 14-17. During gastrulation the bilaminar disc is converted into a trilaminar disc including integration of bilateral notochordal anlagen into a single notochordal process and segmental notochordal formation.


Dorsal induction

Dorsal induction Day 17-28. Formation and closure of the neural tube by primary neurulation. The three primary brain vesicles develop during this period. The mesecephalic flexure develops by day 21 and the cervical flexure develops by day 28. The pontine flexure forms on day 32.


Secondary neurulation

Secondary neurulation occurs during day 28-48. At this time the neural tube caudal to the posterior neuropore is formed from mesenchyme by cavitation.


Ventral induction

Ventral induction occurs during the 5th to 10th week. The three primary brain vesicles - prosencephalon, mesencephalon and rhombencephalon - differentiation into five vesicles.

Prosencephalon into telencephalon and diencephalon. The rhobencephalon into the metencephalon and myelencencephalon. The mesencephalon stays as is.


Neuronal proliferation and migration

Neural proliferation occurs during weeks 6-12. Neuroblasts proliferate in the subependymal zone of the neural tube adjacent to the central canal of the spinal cord or the ventricles of the brain. Neuronal migration starts around week 8. Neurons use radial glial cell fibers as scaffolds to reach the cortical or subcortical layers.


When do myelination, synaptogenesis and synaptic elimination occur. 

Myelination starts at 6 months and ends in adulthood.

Synaptogensis starts in week 20.

Synaptic elimination starts 12 months postnatally.


Defects in gastrulation cause:

Defects in gastrulation will affect the development and differentiation of all three primary cell layers and cause abnormalities from the occiput downwards including:

1. Split cord malformations

2. Spina bifida

3. Dermoid and epidermoid cysts.

4. Neurenteric cysts

5. Intestinal duplication

6. Anterior meningoceles


The primitive streak forms when?

Day 14-15. Thus it forms during gastrulation. 

It arises from thickened epiblast/ectoderm.


Dorsal induction includes what processes

Primary and secondary neurulation. The formation of the true notochord and neural tube. 


Fusion of the neural tube first occurs where

At the level of the 4th somite which represents the future CCJ.


The anterior and posterior neuropores close when 

Day 24-26 and 26-28 respectively. The former will give rise to the lamina terminalis. The latter does not actually represent the most caudal aspect of the spinal cord. That is formed during secondary neurulation. 


The neural crest gives rise to 

Branchial arch derivatives

Dorsal Roots

Dorsal Root Ganglia

Autonomic ganglia

Adrenergic cells


Note that the neural crest is formed from the edges of the neural folds during closure to form the neural tube.


What is disjunction

Occurs after neural tube closure and is the separation of the overlying superficial ectoderm from dorsally migrating mesenchyme which forms meninges and the neural arches of the vertebrae and paraspinal muscles. 


The lower sacral and coccygeal components of the neural tube are formed during 

Secondary neurulation. Days 28-48. This involves canalization of a caudal mesenchymal mass and retrogressive differentiation of the rest of the mass into the tip of the conus medullaris and filum terminale. 


The three primary brain vesicles are formed during 

Dorsal induction


What are the three developmental flexures

The cephalic, cervical and pontine flexures.

The first two are ventral, while the pontine flexure is dorsal in nature. The cephalic flexure occurs first between the diencephalon and mesencephalon. The cervical between the myelencephalon anf spinal cord. The pontine between the metencephalon and myelencephlon. 

These flexures are all formed by te 8th week.


Disorders of ventral induction result in

Holoprosencephaly, olfactory aplasia, agenesis of the corpus callosum, agenesis of the septum pellucidum, septo-optic dysplasia and vermian dysgenesis/Dandy Walker spectrum disorders. 


The diencephalon gives rise to

The thalamus, hypothalamus, epithalamus, optic cups, mamillary bodies, and neurohypophysis


Migration of granule cells of the cerebellum takes place along

Bergman radial glia


Mossy fiber input is from 

brainstem nuclei


Climbing fiber input is from

Inferior olivary nuclei


The cerebellum develops between weeks 



What are the roles of SHH, Wnt, FGF8 and BMP4/7 in development

SHH: secreted by the notochord and floor plate - downregulates PAX3 and 7 expression in the midline and ventral half of the neural tube. Dorsoventral patterning.

Wnt - dorsoventral patterning. Active in the midline and dorsal portion of the neural tube.

FGF8 - secreted by the anterior neural ridge and induces brain factor 1 expression to induce telencephalon formation.

BMP4/7 maintain PAX expression in the dorsal neural tube and promote alar plate formation. 


What are the four major layers in the developing neural tube

Central Canal

Ventricular layer - produces neural cells, then glia then ependymal cells. All other layers come from this layer

Mantle layer - contains post-mitotic neurons, will form the gray matter

Marginal layer - contains axons of neurons, will form the white matter. Initially the outermost layer, developmental folding will take it subcortical in position. 


Commisural formation

Commissural formation takes place from weeks 7-9. The commissures form from the commissural plate which is a thickening at the cranial end of the telencephalon. The anterior commissure forms first, then the hippocampal commissure then the corpus callosum (genu first, splenium last)


The spinal cord grey matter is formed form neurons within the ______ layer  during embryogenesis

Mantle layer


Neurons in the mantle layer of the developmental spinal cord develop into .....

In week 4 the neurons in the mantle layer of the spinal cord develop into the alar columns dorsally and the basal columns ventrally. These meet laterally at the sulcus limitans, dorsally the alar columns form the roof plate and ventrally the basal columns form the floor plate.




The alar columns become..

 The alar columns which are dorsal will eventally become the association neurons, receive afferent neurons and develop reflex arcs.