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BMS 249 - Developmental Neurobiology > Axon Guidance I > Flashcards

Axon Guidance I Flashcards

1
Q

How many connections are in the brain?

A

10^14

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2
Q

What was Weiss’s hypothesis about the connectivity in adults?

A

RESONANCE THEORY

  • Random connections and diffuse neuronal outgrowth occurs to all targets
  • Followed by elimination of non-functional connections
  • Activity of the neuron reinforces connection
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3
Q

When did Weiss state his hypothesis?

A

1928

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4
Q

What was Sperry’s hypothesis about the connectivity in adults?

A

CHEMOAFFINITY HYPOTHESIS

  • Directed and specific axon outgrowth occurs through axons, following “individual identification tags” carried by “cells and fibres” of the embryo
  • Chemicals are followed by growth cones
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5
Q

When did Sperry state his hypothesis?

A

1939

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6
Q

What is the superior colliculus termed in the Xenopus?

A

The tectum

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7
Q

When an object is seen, what happens as the image passes through the lens?

A

It is flipped, so that on the retina, the image is upside-down and back to front

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8
Q

How is the upside-down image on the retia flipped the correct way again?

A

The connections from the retina are organised so that:

  • The axons from the nasal side of the retina (more ANTERIOR) go to the POSTERIOR of the tectum
  • The axons from the temporal side of the retina (more POSTERIOR) for the ANTERIOR of the tectum
  • There is a graduation of axons, corresponding topological mapping of the retina in the tectum, forming a fine map
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9
Q

What was the experiment done by Sperry to show that his hypothesis was correct?

A
  • Cut optic nerve and removed temporal part of the retina (so that ONLY nasal axons can grow back)
  • The regrowing nasal axons grew through but ignored the territory of the temporal axons
  • He also ablated the edges of both the nasal and temporal neurons retina, only leaving the central retina
  • Neurons grew back
  • Shows that the mapping of the retinal ganglion in the tectum was graded
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10
Q

What would happen to the nasal neurons in Sperry’s experiment, if Weiss was correct?

A

The nasal neurons would grow everywhere and then be ‘pruned’ back

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11
Q

What did Sperry’s experiments show and not show evidence for?

A
  • Neuron growth during axon regeneration

- Not what happens in the developing embyro

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12
Q

In regards to axon outgrowth, what happens in the embryo?

A
  • Patterns of axon outgrowth which is highly organised. reproducible and stereotyped
  • In the mouse, drosophila, zebrafish and human
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13
Q

What experiment was done to test if a specific neuron knew where to grow?

What was the control for this experiment?

A
  • Reverse part of the spinal cord between T7-LS3 and see if the axons still know where to grown
  • The motor axons still knew where to find their way to their muscle targets
  • Showing that axons navigate to their targets and different neurons know where to send their axons

Control: Taking out this part of the spinal cord and putting it back in the same way

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14
Q

What are guidance cues?

A

Factors in the environment of a neuron which axons use to find their correct targets

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15
Q

What is a growth cone?

A

The growing tip of the axon which senses guidance cues in the environment

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16
Q

Who proposed the growth cone?

A

Cajal

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17
Q

Why were insects used to identify the location of guidance cues?

A
  • Relatively simple nervous system
  • Easy to observe and manipulate
  • Can ablate the cells using lasers (in grasshoppers)
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18
Q

What did Corey Goodman discover?

A

In the grasshopper, identified almost every neuron in the embryonic nerve cord and draw a map of axon projections

19
Q

How are development pathways in embryos the same?

A

Stereotyped from embryo to embryo and from segment to segment

20
Q

Where can guidance cues be found?

A

On axons

21
Q

What happens when a growth cone encounters an axon?

A
  • Pathways change when axons encounter SPECIFIC axons

- Happens in a reproducible way

22
Q

What is the ‘labelled pathway hypothesis’?

A
  • Early axons (pioneers) form an axons scaffold on which later axons (followers) can extend
  • Pioneer axon surfaces express some sort of guidence cue on their surface
  • Axons join specific fasicles based on the type of cell adhesion they express
  • Axons selectively fasciculate together (not random)
  • Different axons carry different receptors for these cues
23
Q

Where are subplate neurons found and what neurons do they provide scaffold for?

How is this proved?

A
  • Project away from the cortes to the thalamus prior to the innervation of the cortex by the LGN neurons
  • If ablate subplate neurons in area 17 before the LGN neurons extend - LGN neruons do not innevate this area
  • Shows that the LGN neurons use the subplate neurons to EXTEND and use at GUIDANCE to get to the right place in the cortex
24
Q

What do pioneer neurons supply for follower neurons and how?

A

A surface for them to extend on and provide guidance to get to the right places

They have guidance cues on their surface, which the receptors on the growth cone interact with to form facicles

  • Contact attraction
25
Q

How do the pioneer axons find their way to the target in an apparently ‘featureless’ environment?

A
  • Different groups of cells are localised in different places in the environment and express DIFFERENT SETS OF TRANSCRIPTION FACTORS (cells are molecularly different)
26
Q

What are the characteristics of pioneer axon pathways?

What do their growth cones do?

A
  • Stereotyped

- Growth cones react at specific points in the pathway?

27
Q

In the grasshopper limb, what happens to the Ti1 (pioneer) growth cone?

A
  • They make a specific turn at the limb boundary

- Then again, a specific turn again as it approaches a specific cell (Cx1)

28
Q

What happens in the grass hopper limb when Cx1 cell is ablated?

A

The Ti1 axon growth cone stalls at the other side of limb boundary - cannot cross the limb boundary (doesn’t turn towards Cx1)

29
Q

Where is Cx1 present in the grasshopper limb?

A

The other side of the limb boundary to the cell body of to Ti1

30
Q

Does Cx1 have any obvious morphological features?

A

No

31
Q

What happens when ‘stepping stones’ or ‘guidepost cells’ are ablated?

A

Stalling of a growing axon

32
Q

Where do the molecular differences in the environment come from, which guide pioneer axons to the correct place?

A

Earlier patterning events in the early embryo

33
Q

What pathways do axon tracts in the forebrain do?

A
  • Tracts avoid, go around and are attracted to specific regions of the brain which are defined by Pax6
  • Follow the boundaries of domains of patterning gene expression
34
Q

What defines particular regions of the brain?

A

Transcription factor Pax6

35
Q

What pathways do axon tracts in the hindbrain do?

A
  • Follow the boundaries of the rhombomeres
36
Q

How is the hindbrain compartmentalised?

A

Into rhombomeres, set up by Hox genes

37
Q

What pathways do axon tracts in the spinal cord do?

A
  • Are attracted to and cross the floor plate

- Follow the boundaries of the floor plate

38
Q

What are the 4 forces of axon guidance and describe them?

A

1) Contract attraction
- Axons can fasiculate together

2) Contract repulsion
- Axons can avoid a certain bundle of axons

3) Chemoattraction
- Secreted material attracts growth cones towards them

4) Chemorepulsion
- Secreted material repulses growth cones away from them

39
Q

Where are axon cues located?

A

On other axons and MANY cell types in the early embryo

40
Q

In the grasshopper limb, what suggests that axon guidance cues can be attractive?

A
  • If Cx1 is ablated, the growth cone stalls and doens’t turn
41
Q

In the grasshopper limb, what suggests that axon guidance cues can be repulsive?

A
  • If Cx1 is ablated, the growth cone doesn’t cross the limb boundary, suggesting it is inhibitory
42
Q

What type of guidance is used by guidepost cells and how?

A
  • Contract attraction/contact repulsion

- They have specific guidance cues on their surface

43
Q

How does contact attaction/repulsion occur?

A

Guidance cues on the surface of cells, such that close physical contact is necessary between the navigating axon and the cell expressing the guidance cue

BMS 249 - Developmental Neurobiology (16 decks)

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