Neuro11 - 25 Flashcards
What is important to know about axon growth guidance?
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
Example of axon guidance reprogramming
Commissural axons lose responsiveness to netrins after transit of the midline
How is commissural axons’ sensitivity to the floor plate altered after crossing the midline?
Become sensitive to something repellant from the floor plate - semaphorins called slits
How is commissural axon sensitivity programmed?
Roundabout gene, encoding Slit receptors - high expression in non midline crossing, low levels in crossing, but then sudden increase after crossed (preventing return)
What occurs in Robo mutants?
Slit not detected, axons go back and forth, forming roundabouts
What does Comm do?
Expressed only in crossing neurons, switched off once crossed
What occurs in Comm mutants?
Robo protein expressed at high levels, no neurons cross the midline
What occurs in Comm overexpression mutants?
Neurons everywhere - no Robo
How does Comm control Robo?
Encode trafficking that prevents Robo from reaching PM so growth cone cannot detect inhibitory Slit
What takes the role of Comm in vertebrates?
Rig1 (Robo3)
How do processes stay on, and then get off, the axon scaffold?
Control of fasciculation
What does controlling fasciculation involve?
Homophilic binding by CAMs, i.e. NCAM or Fasciclin II
How is NCAM post-translationally modified in vertebrates?
Polysialylation - addition of a large cloud of polysialic acid
What does polysialylation of NCAM result in?
Reduced adhesion between cells and may alter homophilic interactions and cis/trans interactions of other molecules on cell surface
What animals is Fasciclin II in?
Insects
What does Fas II control?
Defasciculation
What does overexpression of Fas II cause?
Bypass - axons fail to defasciculate, and miss target
What two main types of target selection are there?
Discrete targets and topographic maps (cellular and multicellular)
Outline discrete target selection
I.e. ablation of specific target muscles leads to failure of relevant motor acons to leave main motor trunk at appropriate branch points
What controls the defasciculation of discrete target selection?
Netrins
What controls the adhesion of discrete target selection?
Fas3
What two methods did Sperry consider for topographic mapping target selection?
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
What was the stripe assay?
Grows axons from each side of eye in both anterior and posterior tectum environments
What was the outcome of the stripe assay?
Cells from posterior tectom make a non-permissive factor that repels temporal retinal axons
What causes the stripe assay effect?
Two ephrins, posteriorly high in concentration, anteriorly low; two ephs, temporally high and nasally low
