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AN4017 > L2 Axon Growth & Target Innervation > Flashcards

L2 Axon Growth & Target Innervation Flashcards

1
Q

How is embryonic axonal navigation accomplished?

A

By the axonal growth cone

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2
Q

What is the axonal growth cone?

A

The motile structure at the distal tip of an elongating neuronal axon

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3
Q

What does a growth cone do?

A

It searches for and detects molecular signposts that are displayed throughout developing tissues

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4
Q

What did Harrison and Speidel identify?

A

The growth cone as a key decision-making component during axon growth

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5
Q

GC structure

A

Thin, fan-shaped sheet (lamellipodia) with many long, thin spikes (filopodia) radiating forward to sense the environment

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6
Q

What happens if the GC collapses?

A

Neurons cannot extend the axon

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7
Q

What are crucial for growth cone steering?

A

Cytoskeletal dynamics - actin filaments & microtubules

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8
Q

What two key events are required to sprout a neurite?

A
  • Filopodium adhering to adjacent extracellular structures
  • Microtubules advancing into an adherent filopodium
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9
Q

4 types of guidance mechanisms for axons

A
  • Contact attraction
  • Chemoattraction
  • Contact repulsion
  • Chemorepulsion
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10
Q

What does the growth cone detect as it travels towards its synaptic target?

A

Extrinsic cues

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11
Q

What do surface receptors on the lamellipodia & filopodia detect? And what is the result of this?

A

Detect intrinsic cues - triggers changes in cytoskeletal & membrane dynamics, which turn the growth cone (i.e. navigation)

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12
Q

What is a major target of guidance cue signals?

A

Axon and microtubule filament network

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13
Q

Guidance cues are linked to __ , which activate intracellular signalling pathways.

A

Rho-GTPases

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14
Q

How do Rho-GTPases affect cytoskeletal dynamics?

A

They regulate actin-binding and microtubule-binding proteins, which control the organisation & distribution of actin filaments & microtubules

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15
Q

Examples of repulsive cues

A

Semaphorin3A and EphrinA

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16
Q

How do repulsive cues affect actin polymerisation?

A

Repulsive cues switch on the GTPase RhoA, which reduces GC protrusion and promotes actin depolymerisation

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17
Q

Examples of attractive cues

A

Neurotrophin and Netrin

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18
Q

How do attractive cues affect actin polymerisation?

A

Attractive cues switch on the GTPases Rac1 and Cdc42, which increases GC protrusion and promotes actin polymerisation

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19
Q

A growth cone expresses receptors for both attractive and repulsive cues. True or false?

A

True

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20
Q

What are guidepost cells?

A

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.

21
Q

What happens when Netrin-1 is knocked out in mice?

A

There’s significant misrouting of commissural axons, with many failing to reach the floor plate due to lack of guidance by Netrin-1.

22
Q

Do diffusible members of guidance cue families function in long- or short-range axon guidance?

A

Long-range

23
Q

Why might different axons respond to the same cue differently?

A

Expression of different surface receptors or intracellular signalling molecules

23
Q

Why might different axons respond to the same cue differently?

A

Expression of different surface receptors or intracellular signalling molecules

24
Q

The 2 major groups of guidance cues

A

Canonical and non-canonical

25
Q

The 4 major families of canonical guidance cues

A

Semaphorins, Netrins, Slits, Ephrins

26
Q

Netrins bind to receptors of which families?

A

DCC and UNC5

27
Q

How can attractive effects of Netrin-1 on the GCs of axons, which are mediated by DCC receptors, be converted to repulsive effects?

A

By introducing an UNC5 family member into the neuron

28
Q

What does Netrin bifunctionality depend on?

A

Receptor composition of axon

29
Q

Different forms of Semaphorins

A

Secreted, transmembrane, or GPI-linked

30
Q

What do Semaphorins bind?

A

Plexins and neuropilins (NPN)

31
Q

Slits bind to receptors of which family?

A

Robo

32
Q

How do filopodia act as scouts for less advanced portions of GC?

A

Either by seizing hold of permissive substrates or avoiding inhibitory substrates to reorient GC extension

33
Q

How does guidance cue signalling regulate actin dynamics?

A

By directly or indirectly altering the activity of Rho-GTPases, which regulate actin polymerisation

34
Q

What Rho-GTPase does Netrin receptor DCC activate?

A

Rac

35
Q

Semaphorin receptors activate __ via an adaptor protein, that stimulates exchange of GDP for GTP on the GTPase.

A

Rho

36
Q

What is topographic mapping?

A

Many axonal projections within the brain establish an orderly arrangement of connections within their target field, termed a topographic map

37
Q

How is a smooth and continuous topographic map formed?

A

By neighbouring cells projecting to neighbouring parts of the target

38
Q

What cell type has been widely studied in terms of topographic mapping?

A

Retinal ganglion cells (retina projection to superior colliculus)

39
Q

What was the Chemoaffinity Hypothesis?

A

Molecular tags on projecting axons and their target cells determine the specificity of axonal connection within a neural map (i.e. molecular mapping rather than functional moulding of random connections)

40
Q

Axons from the temporal side of the retina grow towards…

A

the rostral side of the tectum

41
Q

Axons from the nasal side of the retina grow towards…

A

the caudal side of the tectum

42
Q

What did Friedrich Bonhoeffer develop?

A

An in vitro assay called the membrane stripe assay - first demonstration of a role for repellent activities in axon guidance

43
Q

Two major advances in mid 1990’s regarding axon guidance

A
  1. Cloning of two related genes, EphrinA2 and EphrinA5
  2. Development of new methods of axon tract tracing (fluorescent dyes)
44
Q

What receptors do Ephrins bind to?

A

RTK Eph receptors

45
Q

EphrinA binding to EphA induces…

A

growth cone collapse (crucial in R-C mapping)

46
Q

Wnt3a cooperates with __ binding to regulate D-V mapping

A

EphB-EphrinB1 binding

47
Q

EphrinB binding EphB __ growth cones

A

repels (chemorepulsion)

48
Q

EphrinA2/A3 double knockout mice present with…

A

an ASD-like behavioural phenotype

AN4017 (8 decks)

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