lecture 9 motor and sensory neurone devleopment Flashcards
what are the principal steps of neuronal circuit formatio
neurogenesis & migration
axon growth
what cell type differentiation important part of n.syst dev
glia cell
what are some glia cells
schwann cells - form myelin sheaths around axon important for action potential propgation
where do motor neurons devleop from
the neural tube
describe the steps in the formation of the spinal cord
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
what does dorsal root gangion dev from
neural crest progenitors
what do the ventral and dorsal half of the spinal cord develo intro
dorsal - commisural and association neurons
ventral - motor neurons
where are progenitor cells found in the neural tube
initially all cells can divide
later only found at the ventricular surface
by what mechanism is it thought that progenitor vs neural cell fate is decided
asymmetric cell division
cells that get notch - stem cell
what are radial glia cells
bipolar shaped cells
span width of cortex in developing cns
role as primary progenitors that capable of generating neurons astrocytes abd oligodendrocytes
how does notch maintain precursor cell fate
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)
how does nerual differnetiation occur
gradual commitment from the precursor to commited radial glia cell
what controls the gradual loss of progenitor fate
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)
how was the roel of miR-9 in Hes1 oscillations discovered
foudn that both oscillate but complemetary
how does high Hes1 maintain high N-cadherin
high hes1 = no neurogenin
neurogenin act Foxp14 which inh N-cad
what is the role of N-cad in maintaining progenitor pool
N-cad maintain pool of B catenin
which together with TCF TF promote cell cycle genes inc cyclin D
where do the two broad groups of neurons develop from in the spinal cord
sensory neurons - dorsal root ganglia
motor neurons - ventral root gangiaa
how are motor neurons arranged in the spinal cord
AP columns and have defined target identity
what determines the AP position of limbs motorneurons
hox genes downstream of fgf gradients
what signals further organise the patterning of progenitors in the DV axis
BMP in dorsal n.tube (anatgonises ventral Shh)
Shh in floor plate
in opposing gradients
Retinoic acid
how do shh and bmp effect neural progenitors in the DV axis
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
describe the action of the shh and bmp gradients
bmp dorsal inh ventral by noggin shh from floor plate (ventral) inh from dorsal by bmp shh down or upreg TF
what Tf does Shh control
induces Nkx6.1 and Nkx2.2 supresses pax6 (therefore expr dorsal )
what TF antagonises eachother
nkx2. 2 and pax6
nkx6. 1 and Dbx2
what is the action of Nkx6.1
in the absence of nkx2.2 and irk3 trigger MNR2 exoression
which determines motor neurone fate “master regulator”
how are the subpools of motor neurons generated
cascade of TF
what tf determines MN vs interneuron fate
Isl1
what Tf give dorsal id to muscle columns
Lim1
role of lhx3
neuron go to body musculature
where do dorsal root gangion derive from
neural crest cells emanating from the dorsal n.tube
describe the signal network in dorsal root ganglion formation
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
what is neurogenin and what is it comparable to
a drg determinant
myogenin in muscles
what is the experimental evidence for drg formation
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
how is ap patterning of drg formation regulated
at the level of ncc migration
bySemorphins
what is the effect of semamorphins on movement of ncc
repel ncc by collapseretraction of cellular surface
expr in caudal somite halves
explains the rostral movement
what singalling pathway is important in precursor/neuone cell fate
notch
how does notch promote neuron
delta maintains precursor fate
neuregulin drives differentation towards glial
describe the origin and differentiation of the peripheral glia
from ncc
migrate ventral= sensory neurons
the neuregulin = peripheral glia
describe the origin and differentiation of the macroglia
neuroepithelial progenitors cells - radial glia - neurons
gilogenic switch - astrocytes / oligo-dendrocyte precursor cells (OPCs =
NG2 glia)
describe the origin and differentiation of the microglia
hemopoeitic stem cell in yolk sac (mesoderm)
primitive macrogphages
migrate to ev CNS
microglia
