Axonal Growth & Guidance

Question 1

What factors determine axon guidance?

Answer 1

Extracellular signalling, intracellular signalling, growth cone receptors, cytoskeleton rearrangements and changes in transcription in the nucleus + translation

Question 2

Give an example of a short range guidance cue

Answer 2

Direct Contact

Question 3

Give 2 examples of long range guidance cues

Answer 3

Soluble mediators and a concentration gradient

Question 4

Describe the structure of a axonal growth cone

Answer 4

Lamellopodia (“sheet-like”) and filopodia (“finger-like”).

Question 5

Positive growth cue: ____ f-actin assembly and ____ f-actin retrograde flow

Negative growth cue: ____ f-actin assembly and ____ f-actin retrograde flow

Answer 5

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

Question 6

Function of Rho GTPases

Answer 6

Regulate the polymerisation of actin

Question 7

GTPase pathway in axonal growth cone collapse?

Answer 7

Rho -> ROCK -> LIMK -> Cofilin = growth cone collapse

NB: RhoA is a GTPase (protein; ROCK and LIMK are kinases; Cofilin is an actin binding protein)

Question 8

GTPase pathway in actin polymerisation?

Answer 8

Cdc42 -> Arp2/3, N-WASP, Profilin = actin polymerisation

NB: these are all proteins

Question 9

Examples of synaptogenic growth factors (for formation of synaptic terminal)

Answer 9

• Wnt
• neurexin (on growth cone)
• neuroligin (on target cells)

[neurexin binds to neuroligin]

Question 10

Synaptic plasticity in relation to activity throughout life?

Answer 10

Until synapse formation, it is activity independent

After synapse formation, it is activity-dependent (use it-strengthens, or lose it-removed)

Question 11

Positive growth cues?

Answer 11

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

Question 12

Netrin Receptors (growth cone proliferation)

Answer 12

DCC

Question 13

How Netrin influences growth cone AND example

Answer 13

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

Question 14

Experimental Evidence for Positive Growth Cues?

Answer 14

Failure of APP-mediated delivery of Trk A results in no NGF-mediated signalling -> neurons die

NGF antibody in vivo -> Alzheimers phenotype

Question 15

Trk A is the receptor for ___

Trk B is the receptor for ___

Trk C receives ___

Answer 15

Trk A is the receptor for NGF

Trk B is the receptor for BDNF and NT4/5

Trk C receives NT3

Question 16

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 __

Answer 16

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

Question 17

Give some pathways for NCAM

Answer 17

• Non-receptor tyrosine kinase (Fyn)

- Fibroblast growth factor tyrosine kinase (FGF tyrosine kinase)

Question 18

Receptor for Laminins?

Answer 18

Beta-1 integrins

Question 19

Negative, soluble, long-range growth cues?

Answer 19

Long Range

• Netrin
• Semaphorins (e.g. semaphorin III aka collapsin)
• Slit

Short Range
Cell assoc/:
- ephrins
- semaphorins

ECM assoc/:
- chrondoitin sulphate and proteoglycans

Question 20

Example of Netrin in growth cone repulsion?

Answer 20

Trochlear motor neurons migrate from the ventral half of the s.cord dorsally. They are repelled by netrin.

Question 21

Netrin receptors (growth cone collapse)

Answer 21

Netrin (growth cone collapse): DCC and Unc5
Semaphorin: Plexin (Plexin A and Npn)
Slit: Robo-receptors, Com

Question 22

How do growth cones cross the midline using Slit?

Answer 22

Robo = repulsion

Com removes Robo receptor for Slit -> crosses midline via Netrin-> Com prevents crossing again

Question 23

E.g. of Sema’s role during development?

Answer 23

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

Question 24

Example of Ephrin’s role in axonal growth?

Answer 24

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