Lecture 12 Axon guidance 2 Flashcards
How are neurites selected in vitro
MT stability
Competition between neurites
Feedback loop
When is neuron polarity established in vivo?
+ example
As neurons are born
Suggests neurite selection is based and influenced by the cellular environment
e.g. radial glia already polarised apical to basal and polarity preserved as cell divide
Growth cones of what organism are easier to image?
Aplysia
GC sits down more
What are the three domains of growth cones?
C DOMAIN - central
T ZONE - transitional
P DOMAIN - peripheral
What are made from different types of F-actin?
filopodia and lammelipodia
What are filopodia?
Type of protrusion
- Finger-like projections
- Core of long, bundled actin filaments
What are lamellipodia?
Type of protrusion
- Sheet-like structures
- Crosslinks into a net
What is the action of F-actin in growth cones?
Treadmills in resting growth cone
Describe actin treadmilling
Tubulin is dragged sporadically into Filopedia
Flow from periphery to centre
Filaments break up and recycled to tip
What happens to F-actin treadmilling when the cell experiences attractive cue?
Tubulin are dragged more dramatically to filopedia
How do growth cones change direction?
They do not turn They reorganise their MT 1. GC contacts attractive cue 2. F actin treadmilling slows 3. F actin accumulates 4. This stabilises filopodium and drags MT to back of filopodium
Is a substrate sufficient enough to drive forward movement?
NO
What else is needed to drive movement forward?
Stimulus of cue to rearrange cytoskeleton
What part of filopodium is attached to substrate
C domain = palm
Discuss actin treadmilling process before and after attractive cue encountered
- slow undirected growth - resting - max actin flow
- Growth cue encountered - filopedia extension and reorientation of MT - fast directed growth. Accumulation of F actin to stabilise filopodium and drag MT to back of filopodium
- MOLECULAR CLUTCH - slows rearward (back) treadmilling
- ACTIN-TUBULIN LINK - pulls microtubules into the wake of extending filopodium (i.e. back into filopodium)
What can cues do to growth cones? + experiment
attract and repel them
e.g. mix RGC and SN - fasiculate only with own type due to repulsion
What happens when growth cones encounter repelling cue?
Growth cone collapse - STILL ATTACH - retreat and reorganise
F actin is destabilised and get decrease in F actin (opposite to attractive cue)
Example of family of inhibitory cues? Found by?
Semaphorins
Biochem pur of retina showing collapse of sensory axons
Semaphorin types
- membrane bound
2. secreted
Example secreted semaphorin
Sema 3A