morphogenesis Flashcards
describe the early development of the nervous system
starts from ectoderm
notochord induces neural grove formation
area at bottom = floorplate
area closes from middle out => tube (one layer thick) open on both ends
neural crest cells are on top of tube (separate)
what are neuropores?
openings in neural tube at caudal and rostral end
what causes spina bifida?
when the neural tube doesn’t close at the caudal end
entire cord could remain open too
or cord can close and skin doesn’t fill in over it
what elements of the PNS are neural tube in origin?
motor axons - these are cells within the neural tube growing out
preganglionic autonomic neurons - visceral motor - axons come from neural tube
everything else in the PNS is formed by neural crest cells! - includes all sensory cells, ganglia, adrenal medulla, schwann cells
what comes from neural crest cells?
all of PNS except the two exceptions
leptomeninges
bone and cartilage
adrenal medulla
what promotes neural tube development from ectoderm?
bone morphogenic proteins (released by ectodermal cells) is secreted by ectoderm
notocord makes noggin, chrodin and folistatin to inhibit BMPs (bind to it and block it) - allows formation of neuroectoderm
also induces production of sonic hedgehog and noggin in the floorplate
what does sonic hedgehog do?
highly concentrated in notochord
helps signal what is ventral to the developing neural tube
necessary and sufficient
how does the neural tube acquire directionality (ie what indicates directionality to it while it’s developing)?
sonic hedgehog produced by notochord indicates ventral TGF betas (including BMP, dorsalin, vitamin A) indicate dorsal
how does sonic hedgehog become active?
released inactive
undergoes autoproteolysis
amino-terminal fragment = signaling molecule
cholesterol is attached to N-terminus - required for proper diffusion and activity
therefore statins are bad for the developing brain
how does sonic hedgehog work mechanistically? (i don’t think we need to know this)
normally the Shh receptor (patched = PTC) inhibit smoothened (SMO)
when Shh binds to PTC, SMO is released from the inhibition
SMO then activates Gli family of transcription factors (such as zinc finger proteins)
what is the sulcus limitans?
groove between dorsal and ventral sides of spinal cord
describe the development of the brain stem
roof plate stretches
top of tube becomes alar plate - wings out to the side
basal plate moves more medial
so end up with 4 areas - from lateral on one side to lateral on the other: alar plate, basal plate, basal plate, alar plate
what is the difference between basal plates and alar plates?
neurons in alar plates more likely to be sensory
more lateral
neurons in basal plate more likely to be motor - more medial
what are the flexures in the developing brain?
cervical flexure between brain and spinal cord
cephalic flexture between rhombencephalon and mesencephalon
mesencephalon at the level of cephalic flexure
at 6 weeks get pontine flexure too
what is the order of the developing parts of the brain from the top to the spinal cord in the embryo?
at 4 weeks: proencephalon mesencephalon rhombencephalon spinal cord
at 6 weeks: telencephalon diencephalon mesencephalon metencephalon myelencephalon spinal cord
what does the proencephalon develop into?
diencephalon (=> eye) and telencephalon (=> cerebral cortex; bulges out from sides)
what does the rhombencephalon develop into?
metencephalon (=> pons) and myelencephalon (=> medulla)
how is rostral-caudal organization in the brain established?
retinoic acid is concentrated in the cervical area - diffuses - determines which Hox genes are expressed
Hox genes are expressed based on concentration - different set of genes are expressed in different segments of brain stem too
what determines whether a daughter cell migrates away from its parent or remains and produces other daughter cells?
cells have polarized expressions of Notch and Numb (meaning one end of the cells expresses a lot of notch and the other expresses a lot of numb)
if the cell divides “vertically” (so that even amounts of both notch and numb are distributed to each daughter cell) these cells will continue to divide
if the cell divides horizontally (so one cell gets all of the notch, and the other gets all of the numb) then the cell with the notch will migrate away and differentiate and the one with numb will generate more notch and continue to divide
how is it decided whether a cell will be a neuron or glial cell?
if notch remains high and uninhibited, becomes glial cell
if notch is inhibited by binding to something => activation of certain genes => expression of neuronal factors => neuronal precursors
what prevents clumps of neurons from forming?
cells express both notch and delta
allows for lateral inhibition:
notch and delta are inhibitory together - if one has a little more notch, it’ll inhibit the next cell - then one cell becomes a neuron and the adjacent cells become glial cells - so only one cell in the group has to have a bit extra notch and all the cells around it become glia
why are there so many more glia than neurons?
even though the notch/delta process results in a pattern where about every other cell is a neuron, many of those neurons undergo apoptosis during the later developmental processes and so theres many fewer neurons than glia
what prevents clumps of neurons from forming?
cells express both notch and delta
allows for lateral inhibition:
notch and delta are inhibitory together - if one has a little more notch, it’ll inhibit the next cell - then one cell becomes a neuron and the adjacent cells become glial cells - so only one cell in the group has to have a bit extra notch and all the cells around it become glia
why are there so many more glia than neurons?
even though the notch/delta process results in a pattern where about every other cell is a neuron, many of those neurons undergo apoptosis during the later developmental processes and so theres many fewer neurons than glia
what are the three layers of the developing neural tube?
ventricular zone - inside
mantle zone
marginal zone
what are the three layers of the developing neural tube?
ventricular zone - inside
mantle zone
marginal zone
how do the layers of the cerebral cortex develop?
neurons migrate out to outer layer - so unlike spinal cord, the cell bodies of the neurons are on the outside and the white matter is on the inside
progressive levels of migration occur - everything migrates out to layer 1 and displaces the layers that are already there - so layer 6 is actually 2nd layer to come in, and then layer 5 comes in and displaces layer 6 downward toward the ventricular zone (just the edge of the ventricles)
how do the layers of the cerebral cortex develop?
neurons migrate out to outer layer - so unlike spinal cord, the cell bodies of the neurons are on the outside and the white matter is on the inside
progressive levels of migration occur - everything migrates out to layer 1 and displaces the layers that are already there - so layer 6 is actually 2nd layer to come in, and then layer 5 comes in and displaces layer 6 downward toward the ventricular zone (just the edge of the ventricles)
how is cell fate determined?
neural crest cells migrate to lots of different places - are exposed to different factors and these determine what they differentiate into
so if LIF - sensory neuron
if FGF2 - sympathetic progenitor
- if this is then exposed to NGF, will be adrenergic neuron, as opposed to if it’s exposed to ciliary neurotrophic factor, and then you get cholinergic neuron
if stem cell factor, get melanocyte
if glucocorticoids, get chromaffin cell progenitor and then chromaffin cell
how is cell fate determined?
neural crest cells migrate to lots of different places - are exposed to different factors and these determine what they differentiate into
so if LIF - sensory neuron
if FGF2 - sympathetic progenitor
- if this is then exposed to NGF, will be adrenergic neuron, as opposed to if it’s exposed to ciliary neurotrophic factor, and then you get cholinergic neuron
if stem cell factor, get melanocyte
if glucocorticoids, get chromaffin cell progenitor and then chromaffin cell
what does BMP do?
made by ectoderm
must be blocked to allow neural tube to form
once neural tube is formed, promotes development of dorsal aspect of neural tube
what does TGF-beta do?
family of compounds, including BMP, retinoic acid, dorsalin
promote development of dorsal side of neural tube
what do noggin and chordin do?
secreted by basal plate and notochord
inhibit BMP to allow neural tube to form and promote development of basal plate of neural tube
what do notch and numb do?
numb antagonizes notch’s effect on gene transcription
when notch is suppressed, cells keep dividing
what do notch and delta do?
delta is expressed on cell surfaces
interacts with notch on the adjacent cells
inhibits delta expression on that cell
results in adjacent cells having high levels of notch or delta - high notch => glioblast; high delta => neuroblast
allows for neurons and glia to be intermixed
what are basic helix-loop-helix genes (bHLH)?
activation of these contributes to development of a neuron
what inhibits BMP?
noggin, chordin, folistatin
describe the development of the retina (very general)
develops directly from neural tube as an outpouching from the diencephalic vesicle
describe the development of the inner ear (very general)
induced in overlying ectoderm by presence of rhombencephalon
what does the cerebellum develop from?
dorsal lips of the metencephalon
