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Developmental Neuroscience > Neural Induction 2 > Flashcards

Neural Induction 2 Flashcards

1
Q

Where did the search for the neural inducer start?

A

activin

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2
Q

activin

A

member of TGFb family
indices mesoderm
found in mesoderm of early embryos and brain/notochord later

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3
Q

Activin in ectodermal cells

A

bind receptor, dimerises, activates cytoplasmic c kinase domain = signal

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4
Q

activin in ectoderm explants

A

activin bind receptor, signalling occurs

secondary signal from mesoderm converts ectodermal fate to neuonal fate

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5
Q

activin receptor with no signalling domain

A

still bind activin and dimerise but no signal

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6
Q

Experiment - activin receptor

A

mRNA encoding mutant receptor injected into both cells of 2 cell embryo - neural tissue?? would expect epidermal tissue as no signal

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7
Q

finding of truncated activin receptor - neural tissue

A

neural tissue when to active signalling and no secondary signalling from mesoderm

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8
Q

conclusion from truncated activin receptor experiment

A

activin inhibition leads to formation of neural tissue

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9
Q

3 endogenous activin inhibitors

A

follistatin
noggin
chordin

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10
Q

Follistatin - what is it?

A

activin binding protein
inhibits mesoderm producing activity of activin
promotes neural differentiation

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11
Q

where is follistatin found?

A

gastrula stage: mRNA in spemann organiser and neural inducing tissues

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12
Q

Follistatin experiment

A

overexpress follistatin
bin activin and prevent receptor signal
neural tissue

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13
Q

conclusions from follistatin experiment

A

trunacted activin receptor and this experiment - negative role for activin signalling in neural induction

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14
Q

Noggin

A

protein - mRNA in neural inducing tissues

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15
Q

what does noggin bind to and prevent signalling?

A

BMP

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16
Q

Noggin experiment

A

Inject mRNA into ventral blastomere - partial 2nd neural axis induces neural tissue directly from ectoderm

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17
Q

noggin - direct and indirect neural induction

A

ectoderm + purified noggin = direct neural tissue

overexpress noggin = mesoderm intermediate

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18
Q

noggin conclusion

A

noggin present right time and place to be neural inducer

induce neural fate directly or indirectly

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19
Q

chordin - what is it, what does it do and where is it found?

A

protein, binds BMP

mRNA spemann organiser

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20
Q

chordin - direct or indirect?

A

directly induces neural tissue

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21
Q

evidence for chordin, follistatin and noggin working together

A

inhibit 1 = minor neural plae defect
all = substantial defect
stain for sox2

22
Q

similarities of 3 neural inducers

A

present right time and place
soluble proteins
induce neural tissue by blocking BMP binding

23
Q

what does BMP-4 induce?

A

epidermis

24
Q

What is BMP-4?

A

protein - TGFb family
binds to activin receptor
mRNA in ectoderm/epidermis not in spemann organiser

25
Q

BMP-4 experiment

A

inject mRNA - ventralises, mRNA to inhibit BMP-4 dorsalises

inject with mRNA against BMP-4 receptor (ventral injection) - partial second axis

26
Q

what does BMP-4 regulate?

A

dorsal/ventral patterning in xenopus

27
Q

what does BMP-4 inhibit?

A

neural tissue

28
Q

animal cap + BMP-4/mutant BMP-4 findings

A

animal cap + mutant BMP-4 or receptor or BMP-4 inhibitor = neural tissue
dissociate cells - no BMP-4 = neural
+BMP-4 = epidermis

29
Q

challenges to default model

A

neither chordin nor noggin can induce neural tissue if FGF signalling blocked
BMP signalling necessary but not sufficient

30
Q

Evidence - challenge to neural default model

A

inject mRNA BMP antagonist into blastomere contribute to epidermis but not neural plate - no neural tissue
co-inject with FGF = neural tissue

31
Q

What regions of embryo is BMP-4 not produced?

A

those with high nuclear b-catenin (controlled by wnt)

32
Q

Anterior patterning of neural plate

A

activin, follistatin, chordin, noggin, BMP

33
Q

What signals posteriorise neural plate?

A

wnt and FGF

34
Q

ectoderm - what happens if block BMP-4?

A

anterior CNS

35
Q

ectoderm - block BMP-4 and add FGF?

A

posterior CNS

36
Q

wnt

A

class of secreted glycoproteins that regulate b-catenin activity and gene transcription

37
Q

what happens if wnt overexpressed?

A

over-dorsalised embryo

explants undergo neural differentiation

38
Q

evidence wnt posteriorises

A

gradient of nuclear b-catenin high posteriorly

wnt induces hindbrain markers in neurulised animal caps

39
Q

3 models of A/P patterning of neuroectoderm

A

ectoderm pre-patterned - signals from mesoderm
ectoderm homogeneous and mesoderm prepatterned
2 signal model - ectoderm induced to become anterior neural tissue, then posteriorised from posterior mesoderm

40
Q

diffusible factor from roof plate inducing commissural neurons

A

BMPs, dorsalin 1

41
Q

Induction of motor neurons and floorplate by notochord

A

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

42
Q

induction by floor plate

A

notochord between edges of neural folds at time of fusion = floor plate where roof plate should be
extra lateral floor plate = ectopic lateral floorplate

43
Q

what does floorplate secrete?

A

shh

44
Q

what does roofplate secrete?

A

BMP/wnt

45
Q

netrin affect on commissural axons

A

protein in spinal cord stimulate outgrowth of commissural axons
attract axons toward floor plate

46
Q

where is netrin 1 expressed?

A

floor plate

47
Q

where is netrin 2 expressed?

A

ventral 2/3 of spinal cord but not floor plate

48
Q

shh

A

produces protein

ventralising factor in vertebrae spinal cord

49
Q

commisural axons - wnt and shh

A

attracted to floorplate by shh
ventral midline, switch to repulsion, steer growth cones anteriorly
attract anteriorly to wnt

50
Q

Evidence that shh indices floor plate and motor neurons

A

embryos - shh in notochord
shh ectopic = ectopic floor plate
neural tube cells made to express shh - motor neurons

51
Q

how can shh form floor plate and motor neurons?

A

floor plate induction by amino-terminal cleavage product - contact dependent
motor neurons - diffusible factor

Developmental Neuroscience (10 decks)

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