neurulation

neurulation

the early processes that initiate development of the central nervous system

two parts of neurulation

specification of the neural ectoderm (dorsal side of embryo) and morphological change

parts of the central nervous system

brain and spinal cord

what is the cns derived from 

a single cylinder of ectoderm that forms along the dorsal surface of the embryo

what does Sox TFs activate expression of

neural specific genes that result in the differentiation of the neural plate into nervous tissue

where does neurulation initiate

starts at anterior and progresses towards posterior

steps of primary neurulation

1. neural plate forms

2. neural folds and groove forms

3. bending of the neural plate

4. convergence of the neural folds

5. closure of the neural tube

what induces the neural plate formation

BMP inhibitor signals from the node

what gene is required for proliferation in the neural plate

pax3

where does the neural groove form

the center of the neural plate

what cells change shape to bend the neural plate

medial hinge point cells change shape to become wedge shaped (apical constriction)

what cells change shape to cause the convergence of the neural fold

dorsolateral hinge point cells change shape and become wedge shaped

what fuse to close the neural tube

neural grooves

what is the hardest part of neurulation

closure of the neural tube

what inhibition is required for medial hinge point cells

chordin/noggin/BMP inhibition

what signaling is required for formation of dorsolateral hinge point cells

activation of Wnt and repression of Shh

mechanisms of closing the neural tube

altered cadherin expression

what is altered cadherin expression for closure of neural tube regulated by

partially regulated by a TF called Grainyhead, activators of the cytoskeleton called Rac1 and inositol
neural tube - N cadherin
epidermis - E cadherin

how common is neural tube defects

1 in 1000 births

what genetic mutation can cause neural tube defects

mutations in Pax3, Shh, Wnt, and Grainyhead

what environmental factors can cause neural tube closure defects

folic acid deficits and cholesterol metabolism

how many NTD are caused by folic acid deficits

up to half of all human NTDs

why does folic acid deficits impact neural tube closure

its implicated in cellular methylation pathway and required for cell proliferation and gene expression (linked to Pax6)

why does cholesterol metabolism effect neural tube closure

it effects Hh signaling

treatment for spina bifida

only treatment is surgery 

anterior NTDs

anencephaly or craniorachischisis - incompatible with life

what causes anterior NTDs

incomplete formation of part or all the brain

posterior NTDs

spina bifida

Some drugs, such as valproic acid (used to treat epilepsy), act as folate inhibitors. Patients taking valproic acid are advised to stop when they are considering becoming pregnant. Why? What might be the effects of continuing use of valproic acid during pregnancy?

the valproic acid would inhibit folic acid, which can lead to NTDs

how does the neural tube continue to differentiate

a-p patterning and hox genes

how does the spinal cord start

as a single layer of pseudostratified epithelium

what tissue becomes the central canal of the spinal cord

internal lumen

where does spinal cord proliferation happen

ventricular zone - close to the basement membrane

where do differentiating cells from the ventricular zone migrate

move exterior and will differentiate into neuroblasts or glial progenitors  

what part of the neural tube becomes grey matter

middle intermediate zone

what part of the neural tube becomes white matter

marginal zone - where neurons extend axons

if adult stem cells persisted in the spinal cord, where would you expect to find them?

the ventricular zone

what do the cells of the spinal cord differentiate into

neurons (sensory and motor) and glial cells (astrocytes, oligodendrocytes, ependymal cells)

how are the cell types of the spinal cord organized

layers along the d-v axis

step one of neurulation

neural plate forms

step two of neurulation

neural fold and grooves form

step three of neurulation

bending of the neural plate

step four of neurulation

convergence of the neural folds

step five of neurulation

closure of the neural tube