Axon guidance 2 Flashcards
What are filopodia
finger like cellular outgrowths formed of F-actin bundles
What are lamellipodia
Sheet-like actin bundles that are crosslinked into a net
What process is present in the resting growth cone
F-actin treadmills - tubulin is dragged sporadically into the filopodia
What happens when the growth cone comes into contact with an attractive cue
F-actin treadmilling slows
Tubulin is dragged much more dramatically into the filopodia
F-actin accumulates which stabilizes the filopodium and drags microtubules into the back of the filopodium due to an actin-tubulin link
What is the role of semaphorins in growth cone movement
Semaphorins are a family of inhibitory guidance cues
Secreted/soluble semaphorins can cause growth cones to turn or collapse - collapsing effect primarily on F-actin
What are the four forces of axon guidance
Contact attraction
Contact repulsion
Chemoattraction
Chemorepulsion
What is required in order for a growth cone to grow
Axons can’t grow where they can’t attach - however - growth cones need substrates which are permissive for growth - not merely substrates to which they can attach
What is the role of laminin
A growth promoting ECM protein - localised in the optic nerve
Laminin does not dictate the direction of axon growth, merely that axons can grow there
What is the result of of blocking the receptors for laminin
Slows down the growth of retinal axons but does not change their direction
Is laminin permissive for growth at all concentrations
Permissive within a specific concentration range - not permissive at low and high concentrations - permissive but not instructive
What is the role of semaphorins in the developing grasshopper limb -
Non permissive factor- able to channel axon growth (keep it out of regions it isn’t needed)
When semal function is blocked axon growth is sporadic - still reach Cx1 but other processes sent in other directions
What are Ephs/ephrins
Ephrins - cell surface molecules detected by Ephs
Cause repulsion between cells
What role do ephrins have in the developing embryo
Early on it helps compartmentalize the embryo into discrete domains e.g. rhombomeres
What is the role of ephrins in axon guidance
Used to keep axons out of specific areas in ways similar to semaphorins - have a reciprocal pattern of expression in the mammalian embryo
What is the role of chemo attractants/repellents in axon growth
Organisers secrete long distance guiding molecules
What is the role of the floor plate experiment
Experiment 1
Control vs floor plate tissue - showed the floor plate contains a chemo attractant
exp 2
Floor plate placed away from the dorsal spinal cord still saw a response - the floor plate chemo-attractant is secreted
What is the chemo-attractant secreted by the floor plate
Netrin - similar to laminin, can associate with ECM
What is the role of netrin
Necessary for the formation of commissural sensory relay neurons (attraction)
What is the role of the roof plate experiment
Control vs roof plate - axons were repelled away from the roof plate
What is the molecule produced in the roof plate that causes axon repulsion
BMP7 - cells expressing BMP7 mimic the repulsion of the roof plate - Necessary for the creation of commissural axons
How do some C axons reach the floor plate without the presence of netrin
Shh signalling - gradients of morphogens are reused to shape the axon paths - Shh and BMPs co-operate with netrin to guide commissural fibres
