lecture 9 motor and sensory neurone devleopment Flashcards

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1
Q

what are the principal steps of neuronal circuit formatio

A

neurogenesis & migration

axon growth

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2
Q

what cell type differentiation important part of n.syst dev

A

glia cell

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3
Q

what are some glia cells

A

schwann cells - form myelin sheaths around axon important for action potential propgation

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4
Q

where do motor neurons devleop from

A

the neural tube

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5
Q

describe the steps in the formation of the spinal cord

A

first neural plate - nerual cells flanked laterally with epiderm and ectoderm
neural plate folds
neural tube
spinal cord - ncc cells delaminate and the n.tube roof plate cells differentiate

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6
Q

what does dorsal root gangion dev from

A

neural crest progenitors

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7
Q

what do the ventral and dorsal half of the spinal cord develo intro

A

dorsal - commisural and association neurons

ventral - motor neurons

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8
Q

where are progenitor cells found in the neural tube

A

initially all cells can divide

later only found at the ventricular surface

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9
Q

by what mechanism is it thought that progenitor vs neural cell fate is decided

A

asymmetric cell division

cells that get notch - stem cell

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10
Q

what are radial glia cells

A

bipolar shaped cells
span width of cortex in developing cns
role as primary progenitors that capable of generating neurons astrocytes abd oligodendrocytes

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11
Q

how does notch maintain precursor cell fate

A

notch upreg HEs1 and Hes5
these genes down reg proneural genes inc achetate scute complex in dros and neurogenin in verts
hes 5 maintains neuronal precursors
(loss of hes corr with upreg of differentiation markers)

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12
Q

how does nerual differnetiation occur

A

gradual commitment from the precursor to commited radial glia cell

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13
Q

what controls the gradual loss of progenitor fate

A

osciallation of Hes1 maintain progenitor fate
oscillations created by miR-9 which destroy Hes1
but HEs1 act MiR-9 is a negative regulator of itself - anticyclic
cycle breaks as miR-9 increases and reaches threshold then Hes1 down reg - neuronal differnetiation
(additional mech to reg gene expr)

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14
Q

how was the roel of miR-9 in Hes1 oscillations discovered

A

foudn that both oscillate but complemetary

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15
Q

how does high Hes1 maintain high N-cadherin

A

high hes1 = no neurogenin

neurogenin act Foxp14 which inh N-cad

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16
Q

what is the role of N-cad in maintaining progenitor pool

A

N-cad maintain pool of B catenin

which together with TCF TF promote cell cycle genes inc cyclin D

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17
Q

where do the two broad groups of neurons develop from in the spinal cord

A

sensory neurons - dorsal root ganglia

motor neurons - ventral root gangiaa

18
Q

how are motor neurons arranged in the spinal cord

A

AP columns and have defined target identity

19
Q

what determines the AP position of limbs motorneurons

A

hox genes downstream of fgf gradients

20
Q

what signals further organise the patterning of progenitors in the DV axis

A

BMP in dorsal n.tube (anatgonises ventral Shh)
Shh in floor plate
in opposing gradients
Retinoic acid

21
Q

how do shh and bmp effect neural progenitors in the DV axis

A

BMP binds phosphy R-SMAD binds to co-SMAD and translocates to nucleus
shh causes inh PKA, PKA neg reg Gli
neural specification is a function of exposure time and conc of Shh - amount shh specififes fate

22
Q

describe the action of the shh and bmp gradients

A
bmp dorsal
inh ventral by noggin
shh from floor plate (ventral)
inh from dorsal by bmp
shh down or upreg TF
23
Q

what Tf does Shh control

A
induces Nkx6.1 and Nkx2.2
supresses pax6 (therefore expr dorsal )
24
Q

what TF antagonises eachother

A

nkx2. 2 and pax6

nkx6. 1 and Dbx2

25
Q

what is the action of Nkx6.1

A

in the absence of nkx2.2 and irk3 trigger MNR2 exoression

which determines motor neurone fate “master regulator”

26
Q

how are the subpools of motor neurons generated

A

cascade of TF

27
Q

what tf determines MN vs interneuron fate

A

Isl1

28
Q

what Tf give dorsal id to muscle columns

A

Lim1

29
Q

role of lhx3

A

neuron go to body musculature

30
Q

where do dorsal root gangion derive from

A

neural crest cells emanating from the dorsal n.tube

31
Q

describe the signal network in dorsal root ganglion formation

A

wnt upreg neurogenin in prospective drg neurons
SDF1 in path guides CXCR4 expr prospective drg neurons
neurotrophins such as NT-3 exp in dorsal n.tube mediate the survival of drg neurons via TrkC rec

32
Q

what is neurogenin and what is it comparable to

A

a drg determinant

myogenin in muscles

33
Q

what is the experimental evidence for drg formation

A
Constiutive Wnt signal = overgrown drg
ko neurogenin - loss of drg (ectopic - oppo)
invert n.tube - drg shifted 
loss of Neurotriphin - loss of drg
remove CXCR4/SDF - loss of drg
34
Q

how is ap patterning of drg formation regulated

A

at the level of ncc migration

bySemorphins

35
Q

what is the effect of semamorphins on movement of ncc

A

repel ncc by collapseretraction of cellular surface
expr in caudal somite halves
explains the rostral movement

36
Q

what singalling pathway is important in precursor/neuone cell fate

A

notch

37
Q

how does notch promote neuron

A

delta maintains precursor fate

neuregulin drives differentation towards glial

38
Q

describe the origin and differentiation of the peripheral glia

A

from ncc
migrate ventral= sensory neurons
the neuregulin = peripheral glia

39
Q

describe the origin and differentiation of the macroglia

A

neuroepithelial progenitors cells - radial glia - neurons
gilogenic switch - astrocytes / oligo-dendrocyte precursor cells (OPCs =
NG2 glia)

40
Q

describe the origin and differentiation of the microglia

A

hemopoeitic stem cell in yolk sac (mesoderm)
primitive macrogphages
migrate to ev CNS
microglia