Neuronal Movement/Migration Flashcards

(42 cards)

1
Q

True or false: Radial glia span from the outer to the inner surface

A

False: from inner to outer

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2
Q

What is radial migration?

A

The process where neuroblasts migrate by climbing this scaffold of glia.
When they reach their destination, they stop migrating and differentiation is initiated.

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3
Q

What is tangential migration?

A

Long distance neuronal migration from the LGE to the cerebral cortex

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4
Q

What is the Rostral migratory stream?

A

long distance neuronal migration from the SVZ to the olfactory bulb

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5
Q

True or false: Migration of SVZ and LGE cells does not require radial glia.

A

True
o LGE cells migrate tangentially guided by chemical cues.
o SVZ cells migrate rostrally along astrocytic networks.

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6
Q

What do neurons send axons to do?

A

Establish connections with their appropriate target neurons. This is important for synapse formation and for neuronal survival.

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7
Q

What is the growth cone?

A

The only motile part of the axon and has to navigate through a complex climate to reach the target.
The growth cone has to be able to adhere to the route in order to make progress.

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8
Q

Which two kinds of cues allow the growth cone to make a decision about which way to go?

A

Contact mediated and chemotropic guidance cues that are either attractive or repulsive

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9
Q

What causes the physical movement of the growth cone?

A

Dynamic polymerisation and breakdown of actin filaments.

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10
Q

What do actin filaments do?

A
  • Surround microtubules
  • More dynamic than microtubules
  • Drive movement
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11
Q

What do microtubules do?

A
  • extend out through most of the growth cones
  • Stabilise new extended structure
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12
Q

What is the filopodium

A
  • Adhesive, dynamic projection of cytosol
  • Thin projections
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13
Q

What is the lamellipodium?

A
  • Adhesive, dynamic projection of cytosol
  • Sheet like
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14
Q

What do attractive signals do to actin?

A

Stabilise it, so that they elongate towards the signal rather than collapsing

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15
Q

What do repulsive signals do to actin?

A

Destabilise it

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16
Q

What is cytochalasin?

A

It causes shrinking/disruption of actin
Binds to monomeric actin.
Blocks actin polymerization and induces depolymerization of filaments.

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17
Q

What is phalloidin?

A

It disrupts growth cone movement and steering
Stabilises actin filaments and prevents filament depolymerisation
Binds to polymeric actin

18
Q

What causes the penetration of axon growth into tissue?

A

The secretion of proteases that allow the passage of the growth cone
his extension requires microtubules, so when microtubule polymerisation is inhibited axons retract.

19
Q

How can we measure axon growth?

A

Photobleaching.
We would expect new cells to be inserted throughout or to replace bleached area, but it was actually found that new cells were added distally (closer to cone).

20
Q

What are cell adhesion molecules (CAMs)?

A

Molecules expressed by the growth cone that allow it to move.
It does this by modulating adhesion to the extracellular matrix
Provides general cues

21
Q

What does laminin do?

A

It appears to pave many axonal tracts, even if only transiently. Because these are found in multiple places, they can only provide general cues

22
Q

What is haptotaxis?

A

A directional cell movement in response to adhesive substrates such as ECM. Guidance by adhesion gradients

23
Q

What do glycosaminoglycans do?

A

They appear to impede neural outgrowths. They usually prevent adhesion interactions, and can be used to “hide” adhesion substrate and lose traction, preventing elongation.

24
Q

What are the 4 types of CAMs?

A
  1. Sit in cell membrane and bind molecules in membranes of neighbouring cells, e.g. Ig-CAMs, NCAM.
  2. Sit in cell membrane and bind molecules in the extracellular matrix, e.g. Integrins
  3. Localised to specific junctions and bind proteins in similar junctions on neighbouring cells, e.g. Cadherins.
  4. Links to cytoskeleton + secondary messenger signalling pathways affecting cell behaviour (shape, movement).
25
What do cadherins do?
Cadherins mediate homophilic interactions (where two cells have the same molecule). Their action results in the stabilisation of actin by linking to the actin cytoskeleton via catenins.
26
What are cadherins?
They are calcium-dependent, transmembrane, homophilic, act as dimers, and are a major component of adherens junctions. Mediate homophilic interactions
27
True or false: CAMs are homophilic?
They can be both homophilic or heterophilic
28
What do immunoglobulin family CAMs (Ig-CAMs) do?
Drive stabilisation of actin filaments. IgG domains bind to equivalent domains. Calcium dependent.
29
What are integrins?
They are transmembrane proteins, that bind adhesive glycoproteins in the ECM. They are αβ heterodimers and experience calcium dependent binding.
30
How do integrins interact with ECM?
They recognise an arginine-glycine-aspartate sequence in ECM proteins including vitronectin, fibronectin, laminin. Bind adhesive glycoproteins in the ECM
31
Secreted ligand vs membrane-bound ligands for movement
Secreted ligand – cell senses and acts on a graded distribution of the signal. Membrane-bound ligand – form channels that allow or prevent movement
32
What are the 4 guidance mechanism in axon pathfinding that drive directionality?
o Chemorepulsion o Chemoattraction o Contact repulsion o Contact attraction
33
What are the 4 guidance cue families?
* Semaphorins * Netrins * Slits * Ephrins
34
What are pioneer axons?
the first to go out and read cues.
35
What are secondary neurons?
They migrate out and follow the pioneers, they are fasciculated growth cones
36
When does defasciculation occur?
When the contact cues become repulsive and cause the cones to diverge.
37
Where are semaphorins located?
Majority of Semaphorins are membrane bound. Some Semaphorins are secreted and associate with cells or the ECM.
38
What do semaphorins do?
Semaphorins act primarily as repellents but can be attractant.
39
What is the sequence of semaphorins like?
About 20 different proteins – mostly transmembrane Share a distinctive conserved domain of about 500 amino acids
40
Semaphorin receptors
Multiple transmembrane receptors. May alter properties (attract v. repel). Plexins are the transmembrane receptors Transmembrane semaphorins bind directly, but secreted semaphorins require neuropilin to mediate binding.
41
Secretion of semaphorins
About 1/3 are secreted – positively charged carboxy terminus that increases their affinity for the extracellular matrix
42
Secreted (class 2 & 3) or membrane bound ligands (GPI anchored or transmembrane domain) can have repellent or attractive functions (dependent on proteins present in the environment). In the presence of NGF, Sema III has a _ effect on neurite growth. In the presence of NT3, Sema III causes _ of the neurites (NT-3)
repellent, outgrowth