Axonal Growth, Synaptogenesis, and Tropism

Question 1

What is the first step in neuronal identity and the formation of connections?

Answer 1

Polarization

Question 2

Describe the process of polarization?

Answer 2

The neuron starts round with no obvious processes. Over time it begins to extend multiple processes and becomes multipolar. On of the processes becomes an axon which then defines the polarity of the neuron. At the tip of the axon is a specialized structure called growth cone.

Question 3

Cone growth uses both lamellipodia and fillipodia; what are they and what are they used for?

Answer 3

Lamellapodium is a fan shaped sheet at tip of axon. It contains actin filaments and microtubules. Filopodia is a fine process extending out form the lamella podium; contain actin filaments; they form and disappear rapidly.

Question 4

When encountering an attractive cue what happens to the growth cone?

Answer 4

Assembly is increased and retrograde flow slowed causing turning towards the attractive cue (repulsion is the opposite).

Question 5

Which cytoskeletal element modulates direction of growth and which for axon elongation?

Answer 5

Microfilaments (F-actin) dictate direction. Microtubules are responsible for axon elongation

Question 6

There are 4 types of axon guidance signals, what are they?

Answer 6

Non-diffusible (short range) signals: contact attraction and contact repulsion. Diffusible (long range) signals: chemoattraction and chemorepulsion.

Question 7

In the PNS what are some attractive non-diffusible guidance molecules for growth cones?

Answer 7

Collagen, fibronectin, and laminin. These substrates bind to growth cone receptors called integrins, which triggers a series of signaling cascades leading to axon growth and elongation.

Question 8

Which non-diffusible guidance molecule is mostly associated with fasciculation?

Answer 8

Cell Adhesion Molecules (attractive), specifically L1 CAM. They act as a ligand and a receptor. They are Ca independent. They induce cytoplasmic kinases in the growth cone.

Question 9

Cadherins are another example of a non-diffusible attractive guidance molecule, describe how they work:

Answer 9

They are located on the surface of growing axons, growth cones, and surrounding cells or targets. They are a ligand and receptor. They are Ca dependent. The interaction of two cadherins triggers intracellular signaling pathways that lead to actin binding and organization.

Question 10

List the attractive non-diffusible guidance molecules:

Answer 10

CAM, cadherins, collagen, fibronectin, and laminin (the last 3 in the PNS)

Question 11

List the repellent non-diffusible guidance molecules:

Answer 11

Semaphorins (however attractive in some cases), Ephrins

Question 12

What happens when a growth cone encounters a semaphorin?

Answer 12

The ligand/receptor interaction results in growth cone collapse and inhibition of axon extension via receptor interaction with intracellular signaling molecules.

Question 13

What happens when a growth cone encounters a ephrins?

Answer 13

Ephrin interaction with its receptor on the growth cone results in a repellent interaction that collapses the growth cone.

Question 14

What are examples of diffusible guidance molecules? Are they attractive or repellent?

Answer 14

Netrins (attractive or repellent)

Slits (repellent)

Question 15

Where are Netrins secreted? How come they are both attractive and repellent?

Answer 15

They are secreted by target cells in midline of embryo. Attractive receptors are members of the DCC family. Repellent receptors are members the of the UNC5 family. (it depends on the receptor being expressed)

Question 16

What do Slits interact with?

Answer 16

Members of the Robo family. They are always repellent.

Question 17

If Netrin is knocked out what happens?

Answer 17

It eliminates the crossing of comissural axons.

Question 18

Netrin and Slit act in concert at the midline to get comissural axons across, how is this done?

Answer 18

Comissural axons express DCC and are originally attracted to the midline (which produces high levels of Netrin), as they cross the midline they then up regulate Robo which keeps them from recrossing because of the high level of slit at the midline. There is cross talk between Robo and DCC, where Robo signaling inhibits DCC signaling.

Question 19

Describe synaptogenesis at the NMJ

Answer 19

A motor axon makes connate with a myotube (random). After contact both differentiate. Differentiation of the muscle is induced by agrin, which activates MuSK, causing the clustering and increased local expression of acetylcholine receptor (AchR) through rapsyn. Both motor nerve and muscle make ECM components to form a basal lamina which stabilizes the synaptic structure.

Question 20

Synaptogenesis in the superior cervical ganglion involves T1 and T4 axons using the same long-range guidance cues to reach the ganglion, but each innervates a different set of neurons, how is this possible?

Answer 20

Synapse formation is selective and the pre- and postsynaptic neurons have higher affinity for each other. This system of bias in synapse formation guides innervation throughout the nervous system during development without limiting it in any absolute way.

Question 21

Following synaptogenesis what happens to neurons?

Answer 21

They become dependent on their targets for survival and differentiation. Target cells secrete neurotrophic factors that the neurons compete for. Neurons receiving insufficient neurotrophic support degenerate and die.

Question 22

What do target cells play a role in?

Answer 22

They determine the number of cells that innervate them.

Question 23

How does synaptic rearrangement occur during postnatal life?

Answer 23

Neuronal populations are established and trophic interactions continue to modulate synaptic connections. They ensure that each target cell is innervated by the right number of cells.

Question 24

What growth factors do DRGs respond to?

Answer 24

All growth factors

Question 25

What growth factors Nodose ganglia neurons respond to?

Answer 25

NT3 mostly

Question 26

What growth factors do Sympathetic ganglia respond to?

Answer 26

NGF. They do shrivel if near BDNF

Question 27

There are different neurotrohpin receptors, 3 classes of tyrosine kinase receptors and a p75 receptor, what do they respond to?

Answer 27

The TKR’s each bind a distinct subset of processed neurotrophs. They will not bind unprocessed (long) neurotrophs. The p75 receptor binds all unprocessed neurotrophs with high affinity and low affinity for processed.

Question 28

What do neurotrophic interactions depend on?

Answer 28

Neurotrophins secreted by target cells. Neurotrophin receptors on neuron. Intracellular signaling cascades present in neuron

Question 29

What do neurotrophic interaction determine?

Answer 29

Number of neurons. Shape of neurons (degree of arborization). patterns of neuronal connections (number of synapses).