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AN4017 C.A. topics > Axon Growth & Target Innervation > Flashcards

Axon Growth & Target Innervation Flashcards

1
Q

Fundamental cellular unit of the NS?

A

Neuron

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2
Q

What is the growth cone?

A

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

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3
Q

Axons are guided by simultaneous and coordinate actions of 4 types of guidance mechanisms:

A
  1. Contact attraction
  2. Chemoattraction
  3. Contact repulsion
  4. Chemorepulsion
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4
Q

How do axons know when to stop growing?

A

Ephrin binding to Eph-A receptors causes growth cone collapse

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5
Q

What controls the direction of axon growth in the developing brain?

A

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

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6
Q

4 major families of guidance cues

A

Semaphorins, Netrins, Slits and Ephrins

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7
Q

Why are there multiple families of guidance cues?

A

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

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8
Q

What does the floor plate secrete

A

Shh and Netrin

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9
Q

How is embryonic axonal navigation accomplished?

A

By the axonal growth cone

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10
Q

What did Harrison and Speidel identify?

A

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

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11
Q

Growth Cone structure

A

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

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12
Q

What happens if the GC collapses

A

Neurons cannot extend the axon

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13
Q

What are crucial for growth cone steering?

A

Cytoskeletal dynamics - actin filaments & microtubules

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14
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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15
Q

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

A

Extrinsic cues

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16
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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17
Q

What is a major target of guidance cue signals?

A

Axon and microtubule filament network

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18
Q

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

A

Rho-GTPases

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19
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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20
Q

Examples of repulsive cues

A

Semaphorin3A and EphrinA

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21
Q

How do repulsive cues affect actin polymerisation?

A

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

22
Q

Examples of attractive cues

A

Neurotrophin and Netrin

23
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

24
Q

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.

25
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.

26
Q

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

A

Long range

27
Q

Why might different axons respond to the same cue differently

A

Expression of different surface receptors or intracellular signalling molecules

28
Q

The 2 major groups of guidance cues

A

Canonical and non-canonical

29
Q

Netrins bind to receptors of which families?

A

DCC and UNC5

30
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

31
Q

What does Netrin bifunctionality depend on?

A

Receptor composition of axon

32
Q

Different forms of Semaphorins

A

Secreted, transmembrane, or GPI-linked

33
Q

What do Semaphorins bind?

A

Plexins and neuropilins (NPN)

34
Q

Slits bind to receptors of which family

A

Robo

35
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

36
Q

How does guidance cue signalling regulate actin dynamics?

A

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

37
Q

What Rho-GTPase does Netrin receptor DCC activate

A

Rac

38
Q

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

A

Rho

39
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

40
Q

How is a smooth and continuous topographic map formed?

A

By neighbouring cells projecting to neighbouring parts of the target

41
Q

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

A

Retinal ganglion cells (retina projection to superior colliculus)

42
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)

43
Q

Axons from the temporal side of the retina grow towards…

A

the rostral side of the tectum

44
Q

Axons from the nasal side of the retina grow towards…

A

the caudal side of the tectum

45
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

46
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)
47
Q

What receptors do Ephrins bind to?

A

RTK Eph receptors

48
Q

EphrinA binding to EphA induces…

A

growth cone collapse (crucial in R-C mapping)

49
Q

Wnt3a cooperates with __ binding to regulate D-V mapping

A

EphB-EphrinB1 binding

50
Q

EphrinB binding EphB __ growth cones

A

repels (chemorepulsion)

51
Q

EphrinA2/A3 double knockout mice present with

A

ASD

AN4017 C.A. topics (9 decks)

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