AXON GUIDANCE

Question 1

What are the two theories explaining how specific neuronal connections arise in the nervous system?

Answer 1

1.Weiss-resonance theory
random and diffuse neuronal outgrowth
2.Sperry- chemoaffinity hypothesis
direct and specific outgrowth occurs

Question 2

What kind of axon growth is seen in embryos- and which theory does it prove?

Answer 2

Highly organised, reproducible and stereotyped axon outgrowth
SPERRY

Question 3

What evidence supported the idea of guidance cues

Answer 3

Reverse segment of the neural tube in chick embryo
result=
T7 and L1 motor axons still innervate normal muscle targets

Question 4

What are guidance cues?

Answer 4

Factors in the environment that axons can use to find their correct targets

Question 5

What did experiments on grasshoppers conclude?

Answer 5

Labelled- pathway hypothesis
Guidance cues are found on axons
Tested by ablating cells that might carry potential cues and seeing the effects on nearby axons

Question 6

Example of an axon scaffold in vertebrates

Answer 6

The subplate neurons in the mammalian cortex create an axon scaffold- which LGN neurons then use in order to innervate the cortex

Question 7

In developing embryos- where can guidance cues be found?

Answer 7

• In the boundaries of domains of patterning gene expression
• Boundaries of rhombomeres
• Boundaries of the floor plate

Question 8

What are the four forces of axon guidance?

Answer 8

Contact attraction
Chemoattraction
Contact repulsion
Chemorepulsion

Question 9

What are lamella and filopodia?

Answer 9

Two components of the growth cone
Filopodia (extensions)- actin bundles polarised to form larger bundles
Lamella- actin bundles cross linked into a net

Question 10

What occurs when the growth cone encounters an attractive cue

Answer 10

1. Rearward actin treadmilling slows- forward movement of the filopodium
2. Microtubules are pulled into the extending filopodium

Question 11

What is a permissive structure?

Answer 11

Substrates which allow growth cones to grow- do not direct movement

Question 12

What is laminin?

Answer 12

Permissive structure
Growth promoting xtra cellular protein
permissive but not instructive

Question 13

What are non-permissive structures- what can they still do

Answer 13

Contact repellants-

can still channel axon growth

Question 14

What are 2 examples of contact repellants

Answer 14

Semaphorins-
secreted and membrane bound forms
cause growth cone collapse
Ephrins-
early: compartmentalise the embryo into discrete domains
later:keep axons out of specific areas

Question 15

An example of a chemoattractant

Answer 15

Netrin-floorplate protein

Question 16

An example of a chemorepellant

Answer 16

BMP- roofplate protein

Question 17

Which proteins are involved in changing growth cone sensitivites

Answer 17

Robo- Slit

COMM

Question 18

How do the levels of Robo and Comm change in an axon before and after it crosses the floor plate midline?

Answer 18

Robo expressed in high levels after commissural axons cross the midline
Comm expressed in high levels b4 midline (encodes a trafficking protein)

Question 19

How do axons’ sensitivity change to netrins in the floor plate after the midline is crossed?

Answer 19

Sensitivity is decreased

Question 20

How do axons stay on the axon scaffold

Answer 20

Fasciculation to the scaffold-

homophillic binding to CAMs on the scaffold

Question 21

When do axons know when to leave the scaffold?

Answer 21

1. Address labels- specific target molecules
   e. g Netrin- chemoattractant expressed in specific muscles
2. Gradients of ephrins (retinotectal system)- topographic maps

Question 22

What evidence is there for gradients of ephrins (repels temporal retinal axons) in the posterior tectum

Answer 22

1. The activity is abolished by heat treatment of posterior but not anterior membranes
2. Posterior membranes cause temporal growth cones to collapse in vitro

Question 23

What do Fas 2 mutants have?

Answer 23

Many defasciculated axons in ventral cord longitudinal tracts

Question 24

What does over expression of Fas 2 cause?

Answer 24

‘By-pass phenotype’

Motor axons fail to desfaciculate- miss their targets