axon guidance Flashcards

1
Q

how many synaptic connections are there in the human brain?

A

10^14

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2
Q

resonance theory (proposed by Weiss)

A

early, random and diffuse outgrowth to all targets

then elimination of non-functional connections

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3
Q

chemoaffinity hypothesis (proposed by Sperry)

A

directed + specific outgrowth of axons by following individual identification tags carried by the environment

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4
Q

experiment showing chemoaffinity hypothesis is correct

A

cut optic nerve and remove temporal retina, allowing just the nasal axons to extend.
RESULT: nasal axons extends only go to the posterior tectum (where they should go)
IF WEISS WAS CORRECT: nasal axons will grow everywhere and then non-functional axons will be eliminated

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5
Q

experiment showing motor axons can navigate to their targets

A

control = cut and replace segment of neural tube (T7-LS3) before motor axons grow out —> normal innervation of specific limb muscles by motor axons from T7-LS1
cut and reverse T7-LS3 before motor axons grow out —> motor axons still find their way to their normal muscle targets

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6
Q

DEFINE: growth cone

A

growing tip of the axon which senses cues in the environment

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7
Q

DEFINE: pioneers

A

early axons

form an axon scaffold on which followers can extend

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8
Q

DEFINE: followers

A

later axons

extend on an axon scaffold formed by pioneers

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9
Q

Ti1

A

pioneer axon

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10
Q

describe the pathway of pioneer axons in the grasshopper embryo limb

A

Ti1 extends, makes a turn at the limb/body boundary and then turns again to innervate cx1 cell
limb/body boundary contains an inhibitory cue
cx1 cell contains an attractive cue

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11
Q

DEFINE: guidepost cells/stepping stones

A

cells in the pathway of pioneer axons that cause stalling when ablated

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12
Q

what are the 4 different ways guidance cues act in?

A
  • contact attraction
  • contact repulsion
  • chemoattraction
  • chemorepulsion
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13
Q

DEFINE: contact attraction

A

attract when in contact

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14
Q

DEFINE: contact repulsion

A

repel when in contact

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15
Q

DEFINE: chemoattraction

A

attracted to chemicals

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16
Q

DEFINE: chemorepulsion

A

repelled by chemicals

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17
Q

experiment showing the labelled pathway hypothesis is true

A

g axon extends horizontally across midline and makes a turn
ablate p axon –> g axon stalls. other axons still present so not due to lack of axons on which to extend
ablate a axon –> g axon unaffected so not due to reduced number of axons
so p axon carries a guidance cue sensed by g axon growth cone

18
Q

why are aplysia growth cones studied?

A

they are flat so they can be observed easily

19
Q

how is f actin crosslinked in lamella

A

actin bundles crosslinked into a net

20
Q

how is f actin crosslinked in filopodia

A

actin bundles forming larger bundles

21
Q

growth cone when in contact with attractive cue??

A
  • f actin treadmilling slows
  • f actin accumulation near attractive cue
  • microtubules reorganised - establishes new growth direction
22
Q

describe how the cytoskeleton is rearranged during filopodial extension

A
  1. growth cue binds to receptor on filopodium
  2. actin filament crosslinking
  3. actin treadmilling directed towards back slows
  4. actin-tubulin pulls microtubules forward in direction of extending filopodium
  5. forward movement of filopodium towards attractive cue = filopodial extension
23
Q

growth cone when in contact with attractive cue???

A
  • growth cone collapse
  • f actin destabilised –> lower F-actin levels in growth cone
  • actin initiates new growth cones going in a new direction
24
Q

what are semaphorins?

A

inhibitory guidance cues

25
Q

what are permissive substrates?

A

contact attractants

26
Q

how are ephrins used during early patterning?

A

ephrins are non-permissive, contact repulsion ligands
cause repulsion between cells
compartmentalises embryo into discrete domains e.g. rhombomeres

27
Q

what is cre recombinase encoded by?

A

bacteriophage p1

28
Q

what are netrins?

A

chemoattractant secreted by floor plate and muscles
expressed along midline of NS
diffuses through ECM (collagen)
attracts axons towards it
causes commissure axons to turn towards floor plate
enables motor neurons to innervate their muscle targets

29
Q

what is reprogramming growth cones?

A

changing the sensitivity of a growth cone to specific cues as intermediate targets are encountered

30
Q

lipophilic dyes are fluorescent and are absorbed into the membrane to highlight the membrane. what are their possible uses?

A
  • membrane tracking
  • lineage tracing
  • axon tracing
31
Q

what are slits?

A

cell surface repellants expressed in the floor plate

32
Q

what is Robo?

A

receptor for slit

33
Q

what would be observed in a Comm mutant?

A
  • axons do not cross the midline –> no commissures

- increased robo protein levels in axons normally crossing midline

34
Q

what is Comm?

A

trafficking protein preventing robo protein from reaching the cell surface and responding to slits

35
Q

what is Rig1/Robo3?

A

inhibits robo1 signalling in response to slits

expressed only in pre-crossing fibres

36
Q

what would be observed in a Rig1/Robo3 mutant?

A

commissure axons do not cross midline (premature repulsion to slits)

37
Q

what are BEAT proteins?

A

promote defasciculation by disrupting CAM-mediated adhesion e.g. via fascicilin II

38
Q

what is fascicilin 3?

A

homophilic cell adhesion molecule

39
Q

which cues are involved in attracting growth cones to specific targets?

A
  • netrin

- fascicilin 3

40
Q

co-ordinate system for achieving topographic maps

A

encoded by gradients of signalling molecules expressed by the target read by complementary gradients of receptors expressed on axons

41
Q

TRUE OR FALSE: ephrin A2 and A5 are not instructive

A

false

42
Q

describe the stripe assay used to prove the co-ordinate system theory of topographic maps

A
  1. isolated anterior and posterior membranes of the tectum and put them down in alternating stripes in culture
  2. strip of retina placed down the side of alternating stripes
  3. nasal axons extend anteriorly or posteriorly
    temporal axons only extend anteriorly
    gradient of ephrin a2 and a5 expressed in tectum from posterior to anterior
    counter gradient of eph a3 receptors expressed in retinal ganglion cells from temporal to nasal