Axonal Growth & Guidance Flashcards
What factors determine axon guidance?
Extracellular signalling, intracellular signalling, growth cone receptors, cytoskeleton rearrangements and changes in transcription in the nucleus + translation
Give an example of a short range guidance cue
Direct Contact
Give 2 examples of long range guidance cues
Soluble mediators and a concentration gradient
Describe the structure of a axonal growth cone
Lamellopodia (“sheet-like”) and filopodia (“finger-like”).
Positive growth cue: ____ f-actin assembly and ____ f-actin retrograde flow
Negative growth cue: ____ f-actin assembly and ____ f-actin retrograde flow
Positive growth cue: increased f-actin assembly and decreased f-actin retrograde flow
Negative growth cue: decreased f-actin assembly and increased f-actin retrograde flow
Function of Rho GTPases
Regulate the polymerisation of actin
GTPase pathway in axonal growth cone collapse?
Rho -> ROCK -> LIMK -> Cofilin = growth cone collapse
NB: RhoA is a GTPase (protein; ROCK and LIMK are kinases; Cofilin is an actin binding protein)
GTPase pathway in actin polymerisation?
Cdc42 -> Arp2/3, N-WASP, Profilin = actin polymerisation
NB: these are all proteins
Examples of synaptogenic growth factors (for formation of synaptic terminal)
- Wnt
- neurexin (on growth cone)
- neuroligin (on target cells)
[neurexin binds to neuroligin]
Synaptic plasticity in relation to activity throughout life?
Until synapse formation, it is activity independent
After synapse formation, it is activity-dependent (use it-strengthens, or lose it-removed)
Positive growth cues?
Positive, long range growth cues
- Neurotrophins (such as NGF)
- Netrin
Positive, short range:
Cell assoc/:
- Ig superfamily (NCAM)
- Cadherin superfamily (N-cadherin)
ECM assoc/:
- Collagens and Laminins
Netrin Receptors (growth cone proliferation)
DCC
How Netrin influences growth cone AND example
Netrin 1 (steep gradient) and Netrin 2 (shallow gradient)]- can be attractive or repulsive
Commisural neurons in the dorsal half of spinal cord are attracted ventrally by Netrin 1+2
Experimental Evidence for Positive Growth Cues?
Failure of APP-mediated delivery of Trk A results in no NGF-mediated signalling -> neurons die
NGF antibody in vivo -> Alzheimers phenotype
Trk A is the receptor for ___
Trk B is the receptor for ___
Trk C receives ___
Trk A is the receptor for NGF
Trk B is the receptor for BDNF and NT4/5
Trk C receives NT3
Nociceptive neurons with Trk A receptors will extend neurites in the presence of __but will not in the presence of __
Neurons expressing Trk C receptors will extend neurites in the presence of __ but not In the presence of __
Neurones expressing Trk B receptors will selectively respond to __
Nociceptive neurons with Trk A receptors will extend neurites in the presence of NGF but will not in the presence of NT3
Neurons expressing Trk C receptors will extend neurites in the presence of NT3 but not In the presence of NGF
Neurones expressing Trk B receptors will selectively respond to BDNF
Give some pathways for NCAM
- Non-receptor tyrosine kinase (Fyn)
- Fibroblast growth factor tyrosine kinase (FGF tyrosine kinase)
Receptor for Laminins?
Beta-1 integrins
Negative, soluble, long-range growth cues?
Long Range
- Netrin
- Semaphorins (e.g. semaphorin III aka collapsin)
- Slit
Short Range
Cell assoc/:
- ephrins
- semaphorins
ECM assoc/:
- chrondoitin sulphate and proteoglycans
Example of Netrin in growth cone repulsion?
Trochlear motor neurons migrate from the ventral half of the s.cord dorsally. They are repelled by netrin.
Netrin receptors (growth cone collapse)
Netrin (growth cone collapse): DCC and Unc5
Semaphorin: Plexin (Plexin A and Npn)
Slit: Robo-receptors, Com
How do growth cones cross the midline using Slit?
Robo = repulsion
Com removes Robo receptor for Slit -> crosses midline via Netrin-> Com prevents crossing again
E.g. of Sema’s role during development?
Sema III is expressed in the ventral part of the spinal cord.
- NGF-reponsive neurons is repulsed by Sema III -> dorsal s.cord
- NT3-reponsive neurons is not repulsed -> ventral s.cord
Example of Ephrin’s role in axonal growth?
IN RETINAL GANGLION CELLS
Temporal RGCs have high EphA-R -> low EphA in anterior tectum
Nasal RGSs have low EphA-R -> high EphA in posterior tectum
EphA binds to EphA-R -> growth cone collapse
Nasal RGCs w/ less receptors can grow in P.Tectum w/ high Eph R
[Creates topographical map of retina in visual cortex]
NB: used for motor homunculus too
