Development 2 (part 2)

Question 1

4 classes of guidance molecules in axonal pathfinding

Answer 1

secreted by cells:
chemorepulsion
chemoattraction

expressed on cell surface:
contact repulsion
contact attraction

Question 2

4 guidance cue families

- names

Answer 2

semaphorins
netrins
slits
ephrins

Question 3

4 guidance cue families

- locations

Answer 3

secreted + associate with cells/ECM:
netrins
slits
some semaphorins

membrane-bound:
ephrins
some semaphorins

Question 4

4 guidance cue families

- action

Answer 4

attractants/repellents:
netrins

primarily repellents but can be attractant:
slits, semaphorins + ephrins

Question 5

4 guidance cue families

- receptors

Answer 5

for each cue there’s 1 or more transmembrane receptor

Question 6

semaphorins

- features

Answer 6

most transmembrane, 1/3 secreted

conserved semaphorin domain

most repel growth cone
- can have different effects depending on:
> factors in enviro
> different families of plexin or semaphorin

Question 7

semaphorins + plexins

• what are plexins?
• what do they bind to?

Answer 7

= transmembrane protein receptors for semaphorins

transmembrane semaphorins bind directly to plexins

secreted semaphorins need additional protein in order to bind to plexin

Question 8

split proteins

- features

Answer 8

large secreted proteins

3 types in mammals

repulsive

bind to SAX3 or Robo receptors

signal into cell -> changes actin

Question 9

slit proteins

- role in axon guidance

Answer 9

at the midline of the spinal cord

Robo expressing axons run longitudinally + never cross midline

Robo mutant axons cross midline

Commissural axons up-regulate Robo after crossing the midline

Question 10

netrins

- features

Answer 10

diffusible proteins

attractive or repulsive

strong homology to region of laminin-1

Question 11

netrins

- attraction and repulsion mediation

Answer 11

attraction mediated through DCC or UNC-4- receptors

repulsion mediated through UNC-5 receptors

Question 12

ephrins

- classes

Answer 12

class A
- tethered to cell surface by GPI linkage 

class B
- tethered to surface by transmembrane domains

Question 13

ephrins

• clustering
• receptors

Answer 13

must be clustered to activate receptors

RTKs that bind specifically to Class A or B

Question 14

eprhins

- EphA receptors

Answer 14

bind + activate Ephexin

• > binds to rho family GTPases
• > increases rate of actin polymerisation at growth cone leading edge

Question 15

ephrins

- EphB receptors

Answer 15

signal through PDZ-containing proteins including GRIP-1 + a G-protein regulator

Question 16

topographical map formation in retinal-tectal projection

Answer 16

EphrinA2 = smooth gradient across whole tectum

EphrinA5 = steeper gradient in posterior half
-> greater repulsive effect