10. Cell Interactions in Neural Development Flashcards
following neurulation how many population of neurons are specified
3
name the 3 populations of neurons specified after neurulation
- commissural neurons
- dorsal root ganglian neurons (sensory neurons)
- motor neurons
describe the process of lateral inhibition
one cells response to a stimulus is inhibited by excitation of a neighbouring cell
this prevents two cells from acquiring the same cell fate
what inhibits the neural fate in the neuroectoderm
notch
what do all cells in the proneural cluster express
Acheate-scute proteins
which cell develops into the SOP from the pro neural cluster
the one that expresses the most acheate-scute protein
describe the signalling process which is instigated by the one cell that expresses the most acheate-scute
acheate-scute activates expression of delta
delta binds to notch (a transmembrane protein)
notch binding activates the enhancer of split proteins which repress the expression of acheate-scute
this produces a positive feedback loop where eventually only one cell expresses delta
what happens to the cells with no delta
they become epidermal cells
this positive feedback loop escalates acheate-scute production, what happens next in the SOP
levels are high enough to switch on bHLH proteins which commit it as a sensory organ precursor
what drives the movement of the growth cone
actin polymerisation/ depolymerisation
describe chemotaxis
the growth cone responds to chemical signals to determine the direction of movement
name a chemoattractant
netrin
name a chemorepulsant
semaphorins
name a contact attraction molecule
cadherins
name a contact repulsion molecule
ephrins
describe axonal outgrowth in commissural neurons
cell bodies send out axons which migrate ventrally through the floor plate to the other side of the neural tube
what does the floor plate produce
netrin 1
what two types of netrin are found in vertebrates
netrin 1 and netrin 2
what receptor in commissural neurons receives netrin
Unc-40
what does Unc-5 do?
modifies the response of Unc-40
what happens in neurons expressing unc-40 and unc-5
neurons no longer move towards netrin, they change there chemotactic behaviour
what molecule produces clustering of acetylcholine receptors
agrin
how many Ach receptors can one molecule of agrin aggregate
200 Ach receptors
what does agrin bind to and how does it work
binds to LRP4/MUSK which activates raspyn through rho/rac
activates raspyn binds to the AchR resulting in aggregation
which part of the growth cone interacts with its immediate environment
the filopodia finger-like projections
where in the neuron is the site of protein synthesis, what is made here
the cell body
the components for growth cone extension are made here
how are proteins for neural extension transported to the growth cone
by anterograde transport in vesicles along microtubules
what are the three domains of the growth cone
the central domain
the transitional zone
the peripheral domain
what is found in the central domain
microtubules, organelles and vesicles
what is found in the transitional zone
an arch of actin that separates domains
what is found in the peripheral domain
actin, filopodia and a lamellipodia like veil
cell adhesion molecules are important in guiding axon development via contact adhesion, name 2
N-CAM
N-cadherin
where is N-CAM found
on the surface of neurons and glial cells
what do N-CAM KO mice show
axon migration defects and motor deficits
how does cadherins bind
vial calcium dependent adhesion at both ends
where are substrate adhesion molecules found
in the extracellular matrix
name 2 substrate adhesion molecules
laminin
fibronectin
what do laminin and fibronectin in the ECM interact with
intern receptors on the cell surface
describe the evidence for the axonal growth of commissural neurons
if you dissect a spinal cord in two, commissural neurons will still want to send neurons to the bottom towards the floor plate. and they will dangle out
what are two receptors for semaphorins
neuropillins and plexin
what do neuropillins need to work
the co receptor plexin is needed as neuropillins have no signal transduction system
wha happens once semaphorin binds to plexin
microtubules are disassembled, actin is depolymerised and the growth cone collapses
give an example of where chemorepulsion occurs
in the spinal cord, the ventral part secretes semaphorin 3 to repel incoming thermoreceptor and nociceptor neurites
name a contact repulsion
ephrins
what distinguishes ephrin signalling from other signalling pathways
it is bi-directional
ephrin signalling is bi-directional, what does this mean?
one signal that instructs the growth cone to collapse
another signal that instructs the cell the growth cone has made contact with to change protein expression on the cell surface
describe the process of retinotopic map formation
nerve cells in the retina send out projections to the tectum.
temporal retinal neurons = high sensitivity to ephrins
nasal retinal neurons = low sensitivity to ephrins and so extend to a higher concentration of ephrins
what are pioneer axons
pioneer axons are sent first, these use external cues to lay the foundations for future axons
follower axons use these as a pathway
what molecule is essential for neurite outgrowth
brain derived neurotrophic factor
what are the receptors for BDNF
tyrosine receptor kinases
what happens in cells without neurite growth factor
poor neurotic outgrowth and neuronal death
what happens when the axon reaches its target
the axon converts into synaptic terminal and acetylcholine receptors cluster
what 3 molecules does the nerve terminal secrete
agrin
aria
acetylcholine
what is the role of aria
stimulates the production of new Ach receptors
what is the role of agrin
aggregates ach receptors
what is the fancy term for neural tube defects
dysraphic defects
what and when are dysraphic defects caused
occur within the first three weeks of gestation and are caused by incomplete closure of the neural tube.
name 2 conditions that are neural tube defects
anencephaly
spina bifida
describe spina bifida and how it is corrected
the spinal cord and its membrane coverings herniate through a defect in the vertebral column
early surgical repair improves chances of survival
what is anencephaly
where a good part of the brain is absent and the skull is wide open - affected infants die in a few days
what gene is implicated in psychopathology, what does this suggest
Netrin 1 receptor (DCC gene)
abnormalities cause neural dysfunction that causes aberrant perceptions (delusions and hallucinations)
name two disorders of neuronal proliferation and migration
microcephaly
lissencephaly
are disorders of neuronal proliferation and migration fatal
no - often result in psychomotor deficits and seizures
what is lissencephaly
a lack of neural folds (brain is smooth)
what is microcephaly
brain and skull are small in size
