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Developmental Neurobiology > Growth Cones > Flashcards

Growth Cones Flashcards

1
Q

How does a neuron grow

A

As it extends, it leaves behind a cytoplasmic trail (axon)

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2
Q

Growth cone defined by cajal

A

Club/battering ram
Endowed by chemical sensitivity which makes it able to arrive to its destination

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3
Q

What are the functions of the growth cone

A

-sensor and motor for axon growth
-perceives and responds to signals in the environment
-Provides motile force for axon and neurite extension
-aids target recognition

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4
Q

How is axon growth directed (what do they prefer?)

A

Growth cones prefer more adhesive substances

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5
Q

What are the substances growth cones show preference for

A

Laminin
Polylysine

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6
Q

How is axon growth directed

A

By diffusible molecules (netrin) which is an attractive cue for axons
Axons grow towards cues

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7
Q

Long range cues examples

A

Chemorepulsion (slit netrins)
Chemoattraction (netrin)

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8
Q

Example of short range cues

A

Contact repulsion (semaphorins,ephrins)
Contact attraction (IgCAMs)

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9
Q

Two dynamic structures in growth cones

A

Filopodia (actin filaments)
Lamellipodia (actin mesh)

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10
Q

What does the central core of the growth cone contain

A

Microtubules
Mitochondria

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11
Q

What are the three regions of the growth cones

A

Central region (microtubule rich)
Transitional region
Peripheral region (F-actin)

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12
Q

What are lamellipodia and filopodia made up of

A

Dynamic bundles of actin and tubulin which continuously polymerise and depolymerise

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13
Q

What is axon treadmilling

A

Actin added to top, removed from the bottom

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14
Q

3 approaches to understand growth cone migration

A

Genetic
In vivo/biochemical
Visualisation

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15
Q

Genetic approach to understand growth cone migration

A

Identify mutations that disrupt axon growth using c elegans and drosophila

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16
Q

In vivo/biochemical approaches

A

Primary cultures of neurons (hippocampal/cortical/retinal)
Add cytoskeletal modifiers

17
Q

Visualisation approaches

A

GFP labelled molecules to visualized growth cone migration

18
Q

Role of growth cone

A

Directs axonal outgrowth

19
Q

Where is the growth cone steered towards

A

Filopodia dilation occurs where the is a greater concentration of diffusable cue, there is more polymerisation

20
Q

Actin polymerisation and depolymerisation

A

Actin added to + (barbed end)
Actin removed from - (pointed end)
Retrograde flow of actin monomers

21
Q

Microtubule polymerisation and depolymerise

A

Tubulin added at + end
Tubulin removed from - end

22
Q

How does net extension occur

A

Polymerisation is greater than disassembly

23
Q

Role of actin depolymerising drugs

A

Slows axonal extension
Prevent growth cone turning

24
Q

What does growth cone turning require

A

Microtubule polymerisation
Engorging filopodium forms the new axon segment

25
Q

What do microtubules polymerise into

A

Filopodia where actin filaments have been stabilised

26
Q

What are microtubule associated proteins

A

TIP proteins for monomer addition (APC/CLASP/EB3)
Destabilizing proteins (Kif 2A, C/SCG10)
Motors (kinesins and dynein)
Severing proteins (spastin/ katanin)
Stabilizing proteins (MAP1b/Tau/DCX)

27
Q

What causes microtubule invasion of filopodia

A

Proteins that bind to actin filaments and microtubules

28
Q

What does growth cone progression require

A

Myosin and interaction with matrix via cell adhesion proteins (CAM/SAM) - which allows adhesion and movement

29
Q

How do growth cones detect cues

A

Receptors on their surface detect guidance factors e.g. netrin/slit

30
Q

Example growth cone receptors

A

Robo (changes as growth cone extends)

31
Q

Stages in protrusion

A

Tip complex activation - bundled actin polymerisation resulting in filopodial extension
Actin capping - creation of dendritic network for protrusion
Actin severing - new barbed ends for growth

32
Q

Stages in retraction

A

Actin bundle and network loss - inactivation of barbed end protractor proteins, inactivation of bundling proteins , severing without polymerisation, retrograde actin flow maintained
Microtubule shrinkage/destabilization- increased catastrophe, decreased rescue

33
Q

Cytosketal regulators which direct growth cone navigation

A

Guidance cues and receptors
Primary responder molecules
Integration (G proteins)
Coordination
Cytoskeletal effectors
Effect

34
Q

Role of GAPs

A

Rho GTP (active) —-> rho GDP (inactive)

35
Q

Role of GEFs

A

Rho GDP (inactive) —-> Rho GTP (active)

36
Q

Robo (roundabout) mutant

A

Axons in wrong direction

Developmental Neurobiology (19 decks)

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