Axon Guidance Flashcards
What were the two major hypothesis of axonal guidance during the first half of the 20th Century.
Molecular view vs Resonance view
What was the molecular view?
A view proposed by John Langley, that molecular cues in the embryonic direct axons
What was the resonance view?
A view proposed by Paul Weiss, that there is initially random outgrowth of axons; electrical activity causes functionally important connections to survive (overproduction then pruning)
What did Roger Sperry do?
He took the eye of an adult frog and disconnected it from the brain. He turned it 180 degrees and found the frog could not catch the fly.
Why was the frog experiment evidence for molecular view?
Even when starting position is changed, axons still go to their targets
What is the current view on axon guidance?
- Initial establishment of connections based on molecular cues in the embryonic environment detected by the growth cone
- Refinement and shaping of connectivity based on electrical activity. Experience (activity) modifies established connections
How do we establish so many specific connections with so little cues?
- Axons reach their targets in discrete steps
- Guidance cues can have different effects depending on the context, such as the type of receptor being expressed and the signaling state of the neuron
- Regulated expression of cues and receptors and combinatorial effects (one receptor can down regulate another receptor)
What are the conclusion from “in vivo” axon guidance studies?
A) Growth cone movement involves phases of extension (small shape) and pauses (larger growth cone with motile filopodia)
B) Growth cone shape and behavior is position specific. In the optic nerve, growth cones spend more time advancing than in the chiasm
What are the four groups of axonal guidance cues?
A) Chemorepulsion
B) Contact repulsion
C) Chemoattraction
D) Contact attraction
What falls under the Immunoglobulin Superfamily? What do they share in common.
A) Ig CAMs
B) Netrin Receptors
C) Receptors tyrosine kinases
D) Slit receptors
They all have at least one immunoglobulin-like domain
Describe Ig CAMs
A) It is a short ranged cue with adhesive properties, signaling function, and can couple with cytoskeleton.
B) It signals via receptor and non-receptor tyrosine kinases
What are netrins?
A) Netrins are chemotropic, soluble guidance cues that can be attractive or repellent depending on the receptor.
B) They found it in the floor plate cells in chicken embryos where it acted as a chemoattractant
What are the netrin receptors we need to know? Why?
DCC mediates attraction
Unc-5 mediates repulsion
What are semaphorins?
These are guidance molecules that are separate from the Ig Superfamily. They can repulsive cues that can be short or long-range.
Where was the repulsive action of semaphorins first characterized?
collapsin-1 (Sema III) caused a collapsing effect in chick growth cones
