axonal growth synaptogenesis and tropism Flashcards
________is the first step in neuronal identity and the formation of connections.
neuronal polarization
what is the first step in neuronal polarization?
extension of neurites .
1 neurite becomes the axon but it is some what random as to which one becomes the axon.
what happens if you cut off the neurite that is to become the axon?
another neurtie will become the axon therefore there is some flexibility as to which neurite is the axon
what are the morphological characteristics of growth cones?
lamella podium ( ruffling membrane at tip of axon containing actin filaments and microtubules) and filopodia ( finger like projections extending from the lamellapodium; contain actin; form and disappear rapidly)
where do growth cones get signals from?
they react to the environment directly rather than reacting to a signal from the nucleus.
how do growth cones react to environment?
they sense calcium in the environment and also have lots of receptors.
__________microtubules have been around longer than ________microtubules
acetylated microtubules have been around longer than tyrosinated microtubules.
what is fasciculation?
when axons travel along one another ( guide each other) and follow each other to chemo attractant and split in the case of chemorepulsion.
_____are primarily responsible for axon elongation
microtubules
f Actin does what?
dictates direction of axon turning
f actin binding to f actin binding proteins does what?
regulates retrograde flow
where are tyrosinated microtubules located ?
they are enriched in lamellipodia
where are acetylated microtubules?
in axons ( only)
where is f-actin?
lamellipodia and filopodia
what is repulsive especially for regeneration after spinal cord injury?
chondritin sulfate ( but it plays a diff role in early development)
_______in the matrix are both diffusible and non-diffusible
proteoglycans
what are L1 cell adhesion molecules important for?
they are attractants important for fasciculation
cadherin is a ______?
homophilic attractant ( they are non-diffusible)
semaphorins are _______? and lead to_________?
repellants which lead to depolarization of actin. ( they are non-diffusible)
_______are bi directional signalers, which are usually repellant and affects actin and ligand. they also play an important role in ________.
Ephrins ( they are non-diffusible)
optic tectum
what projects to the anterior optic tectum?
temporal axons ( lateral part of the axon)
axons from the _____ ________ are repulsed by ephrin in posterior tectum because they express high levels of an Eph receptor.
temporal retina
axons from the ________ _______ are blind to ephrin because they lack a eph receptor.
nasal retina
_____ ______ projects to posterior optic tectum , something else is directing the ________ _______ to the posterior.
nasal axons, nasal axons
_______ is attractive to netrin.
DCC
________ is repellant to netrin.
UNC5
what crosses the spinal cord and can’t cross back?
commissural neurons
DCC is initially expressed in the neural cone which leads to_______?
crossing the spinal cord
up regulation of _________ occurs as soon as commissural neurons cross the spinal cord.
Robo ( receptor)
after comissural neurons cross over and robo is unregulated the receptor for ____ is activated and the neurons are repulsed from crossing over.
slit
robo interacts with DCC to do what?
further silence DCC’s attraction to prevent recrossing over of commissural neurons
how does the initial formation of the PNS synapse occur?
peripheral nerve releases agrin which binds to MusK ( receptor- a tyrosine phosphatase) which activates Ach receptors through the cytoplasmic linker protein rapsyn
How does the CNS synapse form?
We are not yet sure but there are lots of protocadherins in the CNS and it is thought that the homophilic interactions of protocadherins is probably the first step.
what type of cell is critical in determining the number of cells that get innervated and why ?
target cells because they release neurotrophic factors and cells that don’t have enough neurotrophic factor apoptose.
Synapse formation must be _________: the correct pre- and post synaptic neurons have __________ __________ each other
selectiive
higher affinity
T1 and T4 axons use the same ______________ ________ to reach ganglion but each innervate _________ set of neurons
the same long range guidance cues
innervate different set of neurons
describe the innervation of muscle cells at birth?
they are initially poly-innervated
what happens to muscles cells after birth ( in maturity)?
each muscle fiber gets it’s own nerve fiber ( usually occurs but not always)
_____ _______ direct axons to target cells?
guidance molecules
where do axons form synapses?
on selected target cells
how are axonal branching patters refined ( i/e how does a poly-innervated muscle at birth become ( single-ly ) innervated in maturity?
they are refined via competition and synapse elimination
in addition to contributing to the survival of a subset of neurons what else do neurotrophins
they elaborate axonal and dendritic branches to support connections ( the number of synapses formed)
do all cells respond to all neurotrophins?
no, different cells respond to different neurotrophins, except dorsal root ganglia respond to all growth factors
what are some examples of neurotrophins?
Nerve growth factor ( NGF)
BDNF
NT-3
NT 4/5
what growth factor ( neurotrophin) do nodose ganglia neurons respond to most robustly?
NT-3
what growth factor ( neurotrophin) do sympathetic ganglia neurons respond to most robustly and which don’t they respond to at all?
NGF
don’t respond to BDNF
what are Trk receptors and what is their fnc?
tyrosine kinase receptors (which bind to a subset of neurotrophins
what are the 3 Trk receptors?
TrkA TrkB and TrkC
all three Trk receptors only have an affinity for ________
processed (cleaved) neurotrophins
Which neurotrphins activate the p75 receptor?
all of them
p75 has ___ affinity for unprocesed neurotrophins
high
p75 has ___ affinity for procesed neurotrophins
low
What Trk receptor does NGF mainly use?
TrkA
What Trk receptor does NT-3 mainly use?
TrkC
What Trk receptor do BDNF and NT-4/5 mainly use?
TrkB
which neurotrophin is key in activity dependent plasticity?
BDNF
what are the 4 axon guidance signal types?
2 nondiffusible: ( short range) 1. contact attraction 2. contact repulsion
2 diffusible ( long range): 1.chemoattraction 2. chemorepulsion
in the PNS name 3 attractive substrates for growth cones and what do they bind to?
lamins, collagens, and fibronectin
they bind to integrins which triggers a series of signaling cascades leading to axon growth and elongation
the CNS matrix molecules are largely ________? they include________,_______, and _________
repulsive
they include hyaluronan, proteoglycan, and glycoproteins
Cadherins are Calcium independent or dependent? choose one
Cadherins are calcium dependent ( cadbury chocolate depends on calcium)
CAMs are Calcium independent or dependent? choose one
CAMs are calcium independent
