Growth factor signaling, and synaptic refinement

Question 1

How do axons grow?

Answer 1

• When a neuron is developing (a little ball), then it sends off processes called neurites (Neurites are small processes on developing neurons that ultimately grow out into axons or dendrites under the control of growth stimulating or inhibiting factors from their direct extracellular environment sensed by receptors in the growth cone, the tip of the neurite).
• “Growth cone” at the tip: probes environment for cues.
• Steers based on signaling molecules will towards things that are attractive, and away from things that are repulsive.

Question 2

What is a growth cone?

Answer 2

• specialized structure
  -polymerized acting forms filipodia (filaments, long skinny things, can extend in various directions) and lamellipodia (involved in motility and sensing).
• Actin can polymerize and depolymerize very rapidly.

-Filipodia respond to:
-stabilize at attractive cues
-retract at repulsive cues (will tell you “I don’t want to go there)
-can go a long distance

-Tubulin:
-forms microtubules along the axon: structure and transport

Question 3

Cytoskeletal Dynamics:

Answer 3

Green - attractive cue –> actin filament will be stabilized.
Red - repulsive cue –> retract the filopodia by disassembling the actin.
- Ca 2+ influx mediates the response to cues, filopodium is extending it recontacts attractive or repulsive cues.
- Stabilizing filopodium, the microtubules will assemble and stabilize behind that so the axon can continue.

Question 4

Cytoskeletal Dynamics:

Answer 4

Green - attractive cue –> actin filament will be stabilized.
Red - repulsive cue –> retract the filopodia by disassembling the actin.
- Ca 2+ influx mediates the response to cues, filopodium is extending it recontacts attractive or repulsive cues.
- Stabilizing filopodium, the microtubules will assemble and stabilize behind that so the axon can continue.

Question 5

Growth cone guidance

Answer 5

-Axon –> encounter stuff, what’s it going to do?
-If you got axons that are extending out to the body.
Ex: PNS motor neuron: it’s extending out of the nervous system and it’s encountering a nonneural world.

Question 6

First neurons to get out there are?

Answer 6

“Pioneers” bc there is no established road, finding their way to its muscle without neurons there.
It has to make decisions based on whatever cues it finds out there.
“Followers” follow other axons, much simpler. Growth cones on the left are pioneered, the ones bundled with them, they say I want to go with that kind of axon, so I am part of that motor pool, I’m going to follow that axon out to my muscle. (Their life is easier because all they have to do is follow the other axons that are already going)

Question 7

(+) and (-)

Answer 7

Growth cones are either going to the upper right (+) stuff – chemoattractant it goes towards it.

Some other material shown in the bottom right (-) may be repulsive. Axons won’t go this way

In the middle, you can see that follower neurons are going along in this bundle (green + mean), then you get to a place where there are red (-). That’s when they say this particular axon is no longer interested in going with its friend, and it’s going to branch off in a different direction from that bundle.

Question 8

What are the cues?

Answer 8

-EMC proteins (integrins)
- Cadherins
-Ephrins/ Ephs
- Cell adhesion molecules (NCAM)

Question 9

Longitudinal tracts

Answer 9

Longitudinal tracts carry ascending sensory information from the spinal cord and brain stem up to higher brain centers, as well as descending impulses from the brain to the spinal cord, including motor signals.

Question 10

The Early Insect CNS

Answer 10

Two segmental ganglia:
-Two “commissures” per segment –> anterior and posterior
-longitudinal tracts to and from the brain –> white matter in the spinal cord where axons tracts go from tail to nose.

Question 11

Using Genetics: APoG strikes again!

Answer 11

-Axons stained, showing commissures and tracts.