Genes And Pattern Development In The Developing Nervous System

Front 1

Determination of the neuroectoderm

Back 1

ectoderm exposed to BMP-4 becomes epidermal
ectoderm no BMP-4 becomes neuroectoderm
notochord and prechondral plate Noggin & Chordin to bind BMP-4 so not available to overlying ectodermal cells
Ectodermal cells- express transcription factors cause them to differentiate into neural tissue
- Noggin and Choridn controlled by Henson's node (Organiser region in blastopore lip of amphibian blastula)

Front 2

Vertebrate motor neurones

Back 2

notochord induces formation of floor plate of the neural tube by releasing the diffusible protein product of the Sonic Hedgehog gene.
Floor plate express Sonic Hedgehog

Front 3

Inducing Factors or Morphogens;

Back 3

proteins that promote the generation or maintenance of particular cell or tissue types by binding to receptors on the cell membrane, often through their activation of transcription factors. Inducing factors can be attached to cell surfaces or be diffusable.
TGFb family (e.g. BMP-4), sonic hedgehog, neurotrophins (e.g. nerve growth factor [NGF], brain derived neurotrophic factor [BDNF])

Front 4

Transcription factors

Back 4

proteins that bind to the regulatory sites of specific genes or sets of genes and are necessary for their transcription, i.e. they can switch on transcription of genes that produce a certain phenotype.
E.g. Hox, Lim and Pax proteins

Front 5

Homeodomain transcription factor (HD) interactions

Back 5

Class I HD e.g. Pax6, Dbx2 – suppressed by high levels of by sonic hedgehog
negatively inhibits
Class II HD e.g. nkx, nkx2 – turned on by high levels of sonic hedgehog which inhibits Class I HD

Front 6

Retinoic acid

Back 6

Retinoic acid is the inducing factor responsible for rostro-caudal differentiation of the brain
-Developing nervous tissue briefly exposed to retinoic acid becomes rostral but with longer exposure has more caudal characterstics
Rostro-caudal differentiation is brought about by expression of Hox genes

Front 7

Homeotic genes

Back 7

genes that when mutated convert one part (segment) of the body into the semblance of another. The protein products of many (e.g. in the Hox series), but not all of these genes contain a homeodomain

Front 8

Homeodomain

Back 8

a series of about 60 amino-acids, containing many basic residues forming a structure that binds to DNA. Many but not all homeodomain containing genes are involved in development. Examples active in nervous system development include the Hox series, the Lim family and Pax genes (i.e. they are transcription factors)

Front 9

Hox genes

Back 9

a subset of homeotic, homeodomain-containing genes that specify the rostro-caudal axes of the body through an overlapping sequence of expression.

Front 10

FGF8

Back 10

Fibroblast growth factor (FGF8) is the inducing factor responsible for rostrocaudal patterning in the spinal cord- FGF8 produced in mesodermal cells lying near the primative node. Causal mesoderm produced higher concentrations of FGF8 than rostral mesoderm
Rostral-caudal differentiation- Hox genes, Low levels of FGF8 induce expression of Hoxc5 and Hoxc6 while higher levels induce expression of Hoxc8 and Hoxc9.