Axon Growth & Target Innervation Flashcards
(51 cards)
Fundamental cellular unit of the NS?
Neuron
What is the growth cone?
The motile structure at the distal tip of an elongating neuronal axon
Axons are guided by simultaneous and coordinate actions of 4 types of guidance mechanisms:
- Contact attraction
- Chemoattraction
- Contact repulsion
- Chemorepulsion
How do axons know when to stop growing?
Ephrin binding to Eph-A receptors causes growth cone collapse
What controls the direction of axon growth in the developing brain?
Axonal guidance cues
pre and perinatal exposures that alter brain development and therefore alter the levels of guidance cues which will ultimately change the patterns of brain wiring
4 major families of guidance cues
Semaphorins, Netrins, Slits and Ephrins
Why are there multiple families of guidance cues?
We have these multiple guidance cues from multiple families because it lowers the risk of guidance errors and improves the accuracy of wiring of the nervous system rather than relying on a single molecule
What does the floor plate secrete
Shh and Netrin
How is embryonic axonal navigation accomplished?
By the axonal growth cone
What did Harrison and Speidel identify?
The growth cone as a key decision-making component during axon growth
Growth Cone structure
Thin, fan-shaped sheet (lamellipodia) with many long, thin spikes (filopodia) radiating forward to sense the environment
What happens if the GC collapses
Neurons cannot extend the axon
What are crucial for growth cone steering?
Cytoskeletal dynamics - actin filaments & microtubules
What two key events are required to sprout a neurite?
- Filopodium adhering to adjacent extracellular structures
- Microtubules advancing into an adherent filopodium
What does the growth cone detect as it travels towards its synaptic target?
Extrinsic cues
What do surface receptors on the lamellipodia & filopodia detect? And what is the result of this?
Detect intrinsic cues - triggers changes in cytoskeletal & membrane dynamics, which turn the growth cone (i.e. navigation)
What is a major target of guidance cue signals?
Axon and microtubule filament network
Guidance cues are linked to __ , which activate intracellular signalling pathways
Rho-GTPases
How do Rho-GTPases affect cytoskeletal dynamics
They regulate actin-binding and microtubule-binding proteins, which control the organisation & distribution of actin filaments & microtubules
Examples of repulsive cues
Semaphorin3A and EphrinA
How do repulsive cues affect actin polymerisation?
Repulsive cues switch on the GTPase RhoA, which reduces GC protrusion and promotes actin depolymerisation
Examples of attractive cues
Neurotrophin and Netrin
How do attractive cues affect actin polymerisation?
Attractive cues switch on the GTPases Rac1 and Cdc42, which increases GC protrusion and promotes actin polymerisation
guidepost cells?
Axons navigate successive segments on their trajectories to distant targets. Each segment has a group of cells that act as an intermediate target for growth cones of axons. These cells are termed ‘guidepost’ cells.
