Neural Induction pt 2

Question 1

follistatin

Answer 1

activin binding protein. inhibits mesoderm-producing activity of activin and promotes neural differentiation

overexpression induces neural tissue w/o mesoderm signalling

could be a neural inducer through activin inhibition

Question 2

noggin

Answer 2

inhibits bone morphogenic protein signalling
induces neural tissue directly from ectoderm

direct neural induction and indirect neural induction through mesoderm intermediate

Question 3

chordin

Answer 3

stops BMP binding to its receptor
direct induction neural tissue

Question 4

what is BMP-4

Answer 4

epidermal inducer and a neural embryo

Question 5

evidence implicating BMP4 in neural induction

Answer 5

1. BMP4 present at right time in right place to be epidermal inducer
2. SPemman organiser secreted BMP inhibitors
3. neural inhibitor and epidermal inducer:
   dissociated animal cap cells + BMP4 = epidermis, isolated animal cap cells + BMP4 inhibitor = neural

Question 6

challenges to default model

Answer 6

1. chordin and noggin can’t induce neural tissue if fibroblast growth factor signalling knocked down
2. BMP signalling necessary but not sufficient, FGF signals required for BMP antagonists to induce neural markers
3. best suited to amphibian neural induction

Question 7

role of wnt in establishing A/P axis

Answer 7

over expression in animal cap = overdorsalised embryo

evidence wnt posteriorises: gradient of nuclear beta-catenin in early neural plate (high posteriorly) . wnt induces hindbrain markers in neurulised animal caps

Question 8

models for A/P patterning

Answer 8

1) uniform signal coming from mesoderm, acting on pre-patterned ectoderm

2) uniform ectoderm and different inducers and different anterior - posterior positions

3) 2 signal model. uniform ectoderm and uniform signal from mesoderm tells it to become neural tissue. first becomes anterior by actions of noggin, follistatin and then posteriorising signals later (FGF, Wnt)

Question 9

models for Wnt signalling in early development

Answer 9

no wnt signalling
- BMP promotes epidermal fate and represses neural fate through inhibition of FGF
- active FGF signalling induces neural fate

with wnt signalling
- wnt signals promote neural induction by activation FGF and induction of BMP antagonists
- wnt signals attenuate FGF to provide BMP signals that promote neural fate

Question 10

how is dorsal/ventral polarity established in spinal cord?

Answer 10

notochord releases diffusible factors which induce floor plate formation. this factor then induces motor neurons and other ventral neuron types

roof plate forms from fusion of tips of neural fold. diffusbale factor from roof plate induces commissural neurons and other dorsal neuron types

Question 11

induction by notochord: evidence for induction of floor plate and motor neurons

Answer 11

extra notochord = ectopic floor plate and misplaced motor neurons

two adjacent notochords = wider floor plate

motor neurons always form at set distance from the source of inducing signal from floor plate

Question 12

induction by floor plate

Answer 12

if insert notochord between edges neural folds at time of fusion = floor plate where roof plate should be (motor neurons instead of commusural)

extra lateral floor plate = ectopic lateral floor plate

extra dorsal floor plate = ectopic floor plate where roof plate should be (motor neurons where commissaral shouldd be)

Question 13

sonic Hedgehog

Answer 13

homolog of hedgehog

a good candidate as the ventralising factor in the vertebrate spinal cord

Question 14

commissural axons are guided by opposing gradients of Wnt and Shh

Answer 14

steered ventrally towards Shh driven by floor plate
at ventral midline attraction switches to repulsing, steering growth cone anteriorly
attracted anteriorly towards Ant and repelled by Shh

Question 15

gradients of what determine gene expression along D/V axis

Answer 15

BMP (high dorsally)
Wnt (high dorsally)
Shh (High ventrally)

Question 16

evidence that Shh induces floor plate and motor neurons

Answer 16

Shh expressed in notochord during first time it shows inducing activity
if Shh expressed in wrong place experimentally then get ectopic floor plate formation
if neural tube cells made to express Shh experimentally, they become motor neurons

Question 17

how can a Shh induce floor plate and motor neurones

Answer 17

floor plate induction is by the amino-terminal cleavage product of Shh

motor neuron induction by the diffusable animo terminal cleavage product