Lecture 10: NMJ formation Flashcards
what is the strucutural backbbone of axons
microtubules
descrbie microtubules in axons
hundreds of microm
unusually stable
unipolar bundles
what are the tip of axons like
migratory cells
how are axons established
migratory growth cone at tip
as migrate leave behind axon
what are growth cones
the migratory tip of each axon
what is the property of severed growht cone
continue to navigate
what is the principle for spatial preferences with eg
key in lock = certain cells have the relevant receptor for the signal
eg the extension of neurons in the retina of frogs
the rught retina connect to the left tectum and vice versa
give the moleculr details of spatial prefernce example of neurons and retina in frogs
gradient of EphA3 in retina highest in temporal lowest in nasal
gradient of EphrinA2 A5 in tectum highest in posterior
repel eachother
neurons from the temporal (high Eph) to the anterior (low ephirn)
and nasal (lowEph) to posterior (high ephrin)
what are growth cones composed of
mt (stop at neck)
actin (rich at the peripery/sgl fibres)
receptors
how does guidance signalling of axon work
key lock
receptors-singlas
give examples of receptor-signal combination invovled in grwoth cone migration
signal - rec slit -robo (repel) sema3A - neuropilin ephrinB2 - EphB ephrinA - EphA
what ssignal receptors are differentially expressed in the lateral and medial lateral medial column (LMC)
ephrin b2 in medial
ephrin a in lateral
describe how slit-robo controls motor axon establishment
slit is expressed in the floor plate
repel the robo2 positive motor neurones but not the commisural neurones
describe robo1 and robo 3 action
expressed in the commisural neurones
robo1 can repel
robo3 dom negative - couples up with robo1 - makes complex not repel therefore can cross midline
loss of robo3 - preventss midline crossing of the commisural neurones
what diseases have robo3 mutation
HGPPS (horizontal gaze pulsy with progressive scollosis)
cant look left anf right
lots of neruones dont cross midline
what does Sma£A singalling mediate
split into dorsal and ventral nerve branches
expr in the middle of limb bud
repels growth cones (collapse on exposure) = create d/v paths
what other development example in unit has Sema3A
neural crest cells migrating
what creates the dorsoventral paths of neurons
diff tf code
induces diffenetial expression of eph/ephrin
examples of tf od the motor neuron translating to eph/ephrin
Lim1 - Eph A4 (in lmc lateral)
Isl - EphB (in lmc medial)
what is the effect of the Eph/ephrin singals on growth cone
morphogenetic changes
F-actin - give cone directionality = open up space for MT and mdiate signalling
MT - give cone advance - poly/depoly
ko F-actin - no directionality but can still advance
how is the morthogenetic changes of the growth cone different to the migratory cell
use guidance cues to favour poly and stabilisation of MT depending whether attractive or repel cue
what are chanracteristics of actin and mt
actin = unidirectional growth treadmill, proflin inh growht, forminenh of poly , also rewuire enz inc WASP/SCAR
MT - grow and depoly from the + end = why can groqw and collapse back
what cotnrols the activation of Rho in growth cone
Slit and ROBO assembles the GEFS and GAPS
promote
what is the role of Rho
promote distinct morphogenetic events (rac1 - lamellipodia, cdc42 - filopodia, RhoA - contractility) coordiate actin binding regulators (ABPS and MTBPS)
summary for how signal pathway interact with actin
signal pathways interact with GAPS and GEFS - act on actinn binding pr - actin singal = refines actin activity
what is nmj
a highly specialised synaptic cell junction between two tissues
what cell component crucial for nmj formation and maintenance
ECM inc basement mbn pr (agrin,perlecan,laminin,collagen IV and ColQ)
desrcibe role of agrin
is presyn released
required for post synaptic AChR clusters
how - z-agrin released from neuron - anchors to b.mbn - where maintains AChR at post syn sites
describe the molecular detail for how agrin works
agrin instruct the assembly of postsyn machinery
agrin complex with MuSK and LRP4
then binds with raspyn
raspyn scaffold for clustering of AChR (but can not mediate localisation at NMJ)
what laminins are expr at NMJ
all have B2 and Y1
what seen in B2 KO mice
no presyn active zones (a4)
dispersion of presyn vesicles
glial invasion of syn cleft (b2)
lack of postsyn folds
descibe the role of a4 laminin in pre syn active zone
norm expr everywhere but the synaptic areas
= controls the alignment
what is the wt role of b2 laminin in glial invasion
repels glial cells from the invading cleft
what the role of laminin 421
binds to extracellular loop of calcium channels
this links it to the activ zone
the laminin holds the active zone in place
what two broad dev mechanisms does nmj formation use
contact formation between gc and target muscle
reciprocal signalling events using basement mbn as a hub
