Shh in the thalamus

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Why do we know most about shh in spinal cord?

very long

straight

take cross sections anywhere and sees same general principles

In forebrain lots of different structures and changes

Role of shh in thalamus

Specialised cells at TF boundries

opposing gradients meet

broken symmetry

Tfs at boundry set up antagonism that results in third boundry of specialised cells that make a third signal

signal gets out of cells and sets up two gradients

So if the gradient gives three cell types then the initial gradients give many more cell types

- diferrential competence

Thalamus best system where can see this working

A signal illicits a different outcome based on the history

LDA = ligand dependent antagonism

Self restricting - feedback loops

Side view of embryo

Has endoderm and mesoderm - back is developing nervous system

green bit dorsal neural tube - floor plate

red bit ventral

colours relate to bottom - shh promoter region all the different enhancer elements that govern shh expression

Enhancer elements - tissue specific elements that 'turn on' shh expression - in specific place

Shh regulated in different ways

dynamic regulation of shsh probably what has driven evolution of sophisticated brains

Telencephalon unique to vertebrates

forms cortex - higher processing and cognitive function

Markers such as TFs

compare patterns of expression to make educated guesses about how evolved between organisms

Dorsal projection of shh

fingerlike

expands over time

sometimes called ZLI zona limitans thalamica

Or MDO

To show important

knock out Otx and Fez - dont see dorsal projection of shh

Know that Shh can induce its own expression in adjacent tissue- floor plate

also doing this here - combination of boundry and ventral expression of shh

Neurogenin genes

if expressing neurogenin1 become one type of neuron

If expressing AScl1 become a different type etc

evolutionally conserved mechanism

a key point - once the zli forms and shh is expressed in fl projection it begins to signal out - because different history - different competence of TF's - different outcome

once molecule can give many different outcomes if take past history into account

Shh in ZLI is tightly regulated by Wnt

not just setting up thalamus and pre thalamus - also playing a role in brain function and behaviour

Cichlid - big lake - diverse populations of fish - from common ancestor

Brains are diverse - different between sand and rock dwellers - angle of ZLI different - depends of balance of TFs at ZLI

if alter the balance and change angle - becomes a sand/rock dweller

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