Neuro11 - 25

Question 1

What is important to know about axon growth guidance?

Answer 1

They reprogram - after reaching intermediate targets, different responses may be made in the second stage to the same stimulus that was supplied in the first

Question 2

Example of axon guidance reprogramming

Answer 2

Commissural axons lose responsiveness to netrins after transit of the midline

Question 3

How is commissural axons’ sensitivity to the floor plate altered after crossing the midline?

Answer 3

Become sensitive to something repellant from the floor plate - semaphorins called slits

Question 4

How is commissural axon sensitivity programmed?

Answer 4

Roundabout gene, encoding Slit receptors - high expression in non midline crossing, low levels in crossing, but then sudden increase after crossed (preventing return)

Question 5

What occurs in Robo mutants?

Answer 5

Slit not detected, axons go back and forth, forming roundabouts

Question 6

What does Comm do?

Answer 6

Expressed only in crossing neurons, switched off once crossed

Question 7

What occurs in Comm mutants?

Answer 7

Robo protein expressed at high levels, no neurons cross the midline

Question 8

What occurs in Comm overexpression mutants?

Answer 8

Neurons everywhere - no Robo

Question 9

How does Comm control Robo?

Answer 9

Encode trafficking that prevents Robo from reaching PM so growth cone cannot detect inhibitory Slit

Question 10

What takes the role of Comm in vertebrates?

Answer 10

Rig1 (Robo3)

Question 11

How do processes stay on, and then get off, the axon scaffold?

Answer 11

Control of fasciculation

Question 12

What does controlling fasciculation involve?

Answer 12

Homophilic binding by CAMs, i.e. NCAM or Fasciclin II

Question 13

How is NCAM post-translationally modified in vertebrates?

Answer 13

Polysialylation - addition of a large cloud of polysialic acid

Question 14

What does polysialylation of NCAM result in?

Answer 14

Reduced adhesion between cells and may alter homophilic interactions and cis/trans interactions of other molecules on cell surface

Question 15

What animals is Fasciclin II in?

Answer 15

Insects

Question 16

What does Fas II control?

Answer 16

Defasciculation

Question 17

What does overexpression of Fas II cause?

Answer 17

Bypass - axons fail to defasciculate, and miss target

Question 18

What two main types of target selection are there?

Answer 18

Discrete targets and topographic maps (cellular and multicellular)

Question 19

Outline discrete target selection

Answer 19

I.e. ablation of specific target muscles leads to failure of relevant motor acons to leave main motor trunk at appropriate branch points

Question 20

What controls the defasciculation of discrete target selection?

Answer 20

Netrins

Question 21

What controls the adhesion of discrete target selection?

Answer 21

Fas3

Question 22

What two methods did Sperry consider for topographic mapping target selection?

Answer 22

Unique label complementary to a unique target label OR cartesion grid encoded by gradients of signalling molecules, read by complementary gradients of receptors on neurons

Question 23

What was the stripe assay?

Answer 23

Grows axons from each side of eye in both anterior and posterior tectum environments

Question 24

What was the outcome of the stripe assay?

Answer 24

Cells from posterior tectom make a non-permissive factor that repels temporal retinal axons

Question 25

What causes the stripe assay effect?

Answer 25

Two ephrins, posteriorly high in concentration, anteriorly low; two ephs, temporally high and nasally low