Induction & Early Patterning of the Nervous System

endoderm

innermost layer

lining of digestive tract and some glands

mesoderm

middle layer

muscle, bones, connective tissues, dermis of the skin`

ectoderm

outermost layer

epidermis of the skin and all neural tissues

neuroectoderm

formation of neural tissue requires further induction of the ectoderm to form ___, whose formation is induced from signals coming from the mesoderm layer.

gastrulation

mesoderm infolds and lies beneath the ectoderm

• signals from the mesoderm induce the overlying ectoderm to become neuroectoderm

Bone morphogenic protein

aka BMP

• secreted by ectodermal cells

• maintains the epidermal (skin) phenotype of ectoderm

Noggin, chordin, follistatin

___, ___, and ___ are all proteins secreted by the notochord.

• competitive inhibitors of BMP

• allow for neuronal differentiation and formation of neural plate

BMP signaling pathway

1. binds to BMP receptor and dimerizes it

2. Dimerization causes activation and phosphorylation of cytoplasmic protein Smad

3. Smad translocate to the nucleus and inhibits transcription factor Sox (aka inhibits gene products that induce neural differentiation

ultimately leads to epidermal differentiation

neurulation

neural plate folds and rolls up into a neural tube

• complete by 3rd/4th week of human gestation

folds, groove

during neurulation, the neural plate caves in to form two neural ___ as well as the neural ___

neural crest cells

strip of tissue along the lateral margins of neural plate aka in the neural plate border zone

• highly migratory cells

• pluripotent (undifferentiated) cells

PNS

the neural crest cells will end up developing into the ___

BMP, noggin/chordin/follistatin

The formation of the neural plate border zone is induced by the diffusion of noggin/chordin/follistatin and BMP creating a gradient.

• high concentration of ___ means that the cells will turn into epidermis/skin cells

• high concentration of ___ means that the cells will become neural cells

cephalization

process of anterior-posterior patterning of the nervous system using gradient of Wnt and Cerberus

Wnt

__ pathway plays a major role in trunk (posterior/caudal) development

Cerberus

___ inhibits Wnt pathway in the anterior region leading to head and brain development

MHB

midbrain-hindbrain border

engrailed

transcription factor expressed in MHB allowing gradient formation for other transcription factors Gbx2 and Otx2

Otx2

transcription factor differentiating the forebrain and midbrain

Gbx2

transcription factor differentiating the hindbrain

rhombomeres

8 transient segments of developing hindbrain

• #1-#3 controlled by Gbx2

• specified by production of a unique Hox gene in each one of them

floor plate

transient specialized glial structure along the ventral midline of neural tube

• controls neuronal differentiation and axonal guidance (aka if axons cross over or not)

sonic hedgehog

aka Shh

• secreted by notochord and then floor plate glial cells

• induce floor plate formation

• “ventralizes” neural tube via diffusion gradient

Roof plate

• made by ectodermal cells

• BMP production

• give dorsal characteristic to neural tube

Shh signaling pathway

1. binds to patched receptors (PTC)

2. binding inhibits the inhibition patched exerted onto the smoothened receptors (SMO)

3. SMO receptors activate transcription factor Gli1

4. Gli1 initiates neural gene expression

gradient

dorsalization and ventralization of the neural tube is due to a ___ of both BMP from the roof plate and Shh from the floor plate, with different types of neurons being differentiated depending on the concentration and ratio of both molecules.