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Dev Neurobiology extra > Lecture 12 Axon guidance 2 > Flashcards

Lecture 12 Axon guidance 2 Flashcards

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1
Q

How are neurites selected in vitro

A

MT stability
Competition between neurites
Feedback loop

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2
Q

When is neuron polarity established in vivo?

+ example

A

As neurons are born
Suggests neurite selection is based and influenced by the cellular environment
e.g. radial glia already polarised apical to basal and polarity preserved as cell divide

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3
Q

Growth cones of what organism are easier to image?

A

Aplysia

GC sits down more

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4
Q

What are the three domains of growth cones?

A

C DOMAIN - central
T ZONE - transitional
P DOMAIN - peripheral

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5
Q

What are made from different types of F-actin?

A

filopodia and lammelipodia

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6
Q

What are filopodia?

A

Type of protrusion

  • Finger-like projections
  • Core of long, bundled actin filaments
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7
Q

What are lamellipodia?

A

Type of protrusion

  • Sheet-like structures
  • Crosslinks into a net
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8
Q

What is the action of F-actin in growth cones?

A

Treadmills in resting growth cone

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9
Q

Describe actin treadmilling

A

Tubulin is dragged sporadically into Filopedia
Flow from periphery to centre
Filaments break up and recycled to tip

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10
Q

What happens to F-actin treadmilling when the cell experiences attractive cue?

A

Tubulin are dragged more dramatically to filopedia

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11
Q

How do growth cones change direction?

A 
They do not turn 
They reorganise their MT
1. GC contacts attractive cue 
2. F actin treadmilling slows 
3. F actin accumulates
4. This stabilises filopodium and drags MT to back of filopodium
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12
Q

Is a substrate sufficient enough to drive forward movement?

A

NO

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13
Q

What else is needed to drive movement forward?

A

Stimulus of cue to rearrange cytoskeleton

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14
Q

What part of filopodium is attached to substrate

A

C domain = palm

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15
Q

Discuss actin treadmilling process before and after attractive cue encountered

A
  1. slow undirected growth - resting - max actin flow
  2. Growth cue encountered - filopedia extension and reorientation of MT - fast directed growth. Accumulation of F actin to stabilise filopodium and drag MT to back of filopodium
    - MOLECULAR CLUTCH - slows rearward (back) treadmilling
    - ACTIN-TUBULIN LINK - pulls microtubules into the wake of extending filopodium (i.e. back into filopodium)
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16
Q

What can cues do to growth cones? + experiment

A

attract and repel them

e.g. mix RGC and SN - fasiculate only with own type due to repulsion

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17
Q

What happens when growth cones encounter repelling cue?

A

Growth cone collapse - STILL ATTACH - retreat and reorganise

F actin is destabilised and get decrease in F actin (opposite to attractive cue)

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18
Q

Example of family of inhibitory cues? Found by?

A

Semaphorins

Biochem pur of retina showing collapse of sensory axons

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19
Q

Semaphorin types

A
  1. membrane bound

2. secreted

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20
Q

Example secreted semaphorin

A

Sema 3A

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21
Q

What do semaphorins cause?

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A

Collapse of F actin

22
Q

What is essential for axon growth? How was this shown

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A

axon attachment via palm

Embryonic chick DRG neurons cell bodies and axons - Polyornithine sticky, palladium non-sticky

23
Q

Relationships between adhesion and outgrowth

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A

NO RELATIONSHIP

24
Q

What ECM component does DRG stick better to (adhesion)

25
What ECM component is DRG growth better on
Laminin
26
What can permissive factors do? Example
Can define substrate paths in the embryo | Laminin allows RGC to enter tectum - promoting ECM in optic nerve
27
Other name for permissive factors
Contact attractants
28
What do permissive factors not dictate? Shown by
direction - only allow growth 1. block laminin R --> decrease in retinal growth but direction unchanged 2. Gradients of laminin in vitro don't alter growth (if in certain range)
29
Permissive factors are x2
Permissive to allow growth | Not instructive to alter direction
30
What are non-permissive factors often called?
Contact repellents
31
What can non-permissive factors do?
Channel axon growth
32
What does outgrowth depend on in presence of non-permissive factors
Permissive factors
33
Example of non-permissive factor and its function
- semaphorins - tell an axon it can't grow there e. g. Grasshopper limb bud Ti1 --> Cx1 turns at semaphoring zones
34
What occurs in mice lacking Sema 3A
End in wrong territories
35
Therefore, what is axon growth a balance between?
permissive and non-permissive factors
36
What are ephrins?
non-permissive factors used in early patterning and to guide axons
37
What are ephs?
cell surface molecules detected by receptors
38
What do ephs and ephrins cause?
REPULSION between cell
39
What are the ephs and ephrins important for?
- compartmentalisation in early development into distinct domains e.g. rhombomeres - late dev for keeping axon out of specific areas as do semaphorins - making topographic maps - reciprocal patterning
40
Where are ephs restricted to in vertebrate
Proximal distal limb tips
41
Where are ephrins restricted to in vertebrate
Middle
42
What does the floor plate secrete that effects axon growth?
Netrin
43
What do we know key patterning organisers secrete?
ong distance guiding molecules - chemoattractant and chemorepellents These guide the axons (where as short distant just say where can and cant go)
44
What does netrin do?
act as a chemoattractant for axons - makes axons grow towards it
45
Where is netrin expressed
Vert midline of NS
46
What do floor plate cells and cells expressing netrin gene turn on
Commissural axons
47
What does the roof plate secrete that affects axon growth?
a chemorepellent in the form of a BMP - doesn't allow axons to gorw in that direction
48
What does BMP7 cause
Growth cone collapse
49
A combination of what causes axon growth towards floor plate?
Push factor = BMP | Pull factor = Netrin
50
Example of long and short cues working together
Sema 1 cells surface - blocking with AB means axon stays in wrong are Sema 2 secreted - disrupts Ti guidance

Dev Neurobiology extra (6 decks)

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