Lecture 3: Axonal Growth, Synaptogenesis, and Tropism

Question 1

What structure defines the polarity of the neuron? What is at the tip of this structure?

Answer 1

Axon

Growth cone

Question 2

What is the growth cone and what does it do?

Answer 2

• key decision-making structure in axon pathfinding during neuronal development
• explores extracellular env, determines direction of growth, guides extension of axon

Question 3

What two morphological characteristics are present in growth cones?

Answer 3

lamellapodium

filopodia

Question 4

How is a lamellapodium characterized?

Answer 4

• fan-shaped, tip of axon

- contains actin filaments and microtubules

Question 5

How are filopodia characterized?

Answer 5

fine processes extending out from lamellapodia

• contain actin filaments
• form and disappear rapidly

Question 6

What molecule is in both lamellapodium and filapodia?

Answer 6

F-actin

Question 7

Where are tyrosinated microtubules found?

Answer 7

enriched lamellipodia

Question 8

Where are acetylated microtubules found?

Answer 8

axons

Question 9

What process is key to growth cone turning, and regulates retrograde flow?

Answer 9

F-actin binding proteins to F-actin

Question 10

How do microtubules affect the core cytoskeleton in the axon?

Answer 10

stability, strength

Question 11

What are the four types of axon guidance signals? Are the diffusible or non-diffusible?

Answer 11

1. contact attraction - non-diffusible, short range
2. contact repulsion - non-diffusible, short range
3. chemoattraction - diffusible, long range
4. chemorepulsion - diffusible, long range

Question 12

Where do axon guidance molecules bind?

Answer 12

receptors on growth cones

Question 13

What are non-diffusible attractive guidance molecules for growth cones in the PNS? To what do they bind?

Answer 13

• laminins, collagens, fibronectin

- bind growth cone receptors = integrins

Question 14

What are examples of non-diffusible guidance molecules in the CNS? Are these attractive or repulsive?

Answer 14

-aggrecan, hyaluronan, tenascin

repulsive –> inhibit cell movement/axon growth

Question 15

Describe Cell Adhesion Molecules (CAMs)

Answer 15

• located: surfaces (growing axons, growth cones, surrounding cells/targets)
• non-diffusible
• attractive (homophilic binding)
• calcium independent
• facsiculation (bundling) of axons

Question 16

Describe Cadherins

Answer 16

• located: surfaces (growing axons, growth cones, surrounding cells/targets)
• non-diffusible
• attractive (homophilic binding)
• calcium dependent
• actin binding and organization

Question 17

Describe Semaphorins

Answer 17

• secreted or anchored to cell surface
• non-diffusible
• mostly repellant
• growth cone collapse, inhibition of axon extension

Question 18

What are semaphorin receptors on growth cones? How do the surface and secreted forms bind to these receptors?

Answer 18

• plexins
• surface/anchored forms bind directly to plexins
• secreted forms bind neurophilins, which then bind to plexins

Question 19

Describe ephrins

Answer 19

• on cells surface
• non-diffusible
• repellant
• bi-directional signalling molecules

Question 20

How does ephrin A differ from ephrin B?

Answer 20

Ephrin A = GPI-linked to cell surace

Ephrin B = single-pass transmembrane proteins

Question 21

What does it mean that ephrins are bi-directional signaling molecules?

Answer 21

both growth-cone bearing cell and target cell will respond

Question 22

What signaling molecules guide projections from the retina to the optic tectum?

Answer 22

ephs and ephrins

Question 23

Axons in the developing temporal retina make connections with what portion of the tectum?

Answer 23

anterior tectum

Question 24

Axons in the developing nasal retina make connections with which portion of the tectum?

Answer 24

posterior tectum

Question 25

In what fashion are ephrins expressed in the optic tectum?

Answer 25

anterior-to-posterior gradient

Question 26

Describe how ephrins guide the correct projections from the temporal and nasal retina to the optic tectum

Answer 26

- Axons from temporal retina have Eph receptor --> repulsed by ephrin in posterior tectum --> bind anterior tectum - Axons from nasal retina lack Eph receptor = blind to ephrin --> can bind posterior tectum

Question 27

Are netrins diffusible? What are receptors for attractive vs repulsive netrins?

Answer 27

- Diffusible - Attractive receptors = DCC - Repulsive receptors = UNC5

Question 28

Are slits diffusible? Are the attractive or repellant? What are their receptors?

Answer 28

- Diffusible - Repellant - growth cone receptors = Robo family

Question 29

Netrins play a key role in _____ crossing in the developing ______

Answer 29

comissural axon | spinal cord

Question 30

In comissural axon crossing: Comissural axons express 1____ and are originally attracted to the 2____, which produces high levels of netrin. As they cross the midline, they upregulate 3____, which keeps them from 4_____ because of the high levels of 5_____ at the midline.

Answer 30

1. DCC 2. midline 3. Robo 4. recrossing 5. slit

Question 31

If two different axons use the same guidance cues, how is synaptic specificity achieved?

Answer 31

differential innervation of ganglionic neurons

Question 32

How do incoming axons preferentially form synapses on the correct targets?

Answer 32

pre- and postsynaptic neurons have higher affinity for each other

Question 33

Synaptogenesis at the neuromuscular junction: Motor axon makes contact with 1____. Subsequent differentiation of the nerve terminal and myotube is induced by 2____, which activates 3____, causing clustering and increased local exp of 4_____ through the adaptor molecule 5______.

Answer 33

1. myotube 2. agrin 3. Muscle activated kinase 4. acetylcholine receptor 5. rapsyn rapsyn

Question 34

In synaptogenesis at the neuromuscular junction, what do the nerve terminal and myotube differentiate into?

Answer 34

nerve terminal --> motor terminal | myotube --> postsynaptic apparatus

Question 35

In synaptogenesis at the neuromuscular junction, both the motor nerve and the muscle make ECM components to form a _____, which stabilizes the synaptic structure

Answer 35

basal lamina

Question 36

In synaptogenesis in the CNS, ____ helps localize cytoskeletal elements, synaptic vesicles, active zone proteins, and voltage gated Ca2+ channels to the _______

Answer 36

Neurexin | presynaptic membrane

Question 37

In synaptogenesis in the CNS, ____ recruits neurotransmitter receptors and other postsynaptic proteins to the ______

Answer 37

neuroligin | postsynaptic membrane

Question 38

How do target cells support survival and differentiation of neurons after synaptogenesis?

Answer 38

secrete neurotrophic factors in limited amounts - neurons compete - target cells help determine the # of cells which innervate them

Question 39

Nerve growth factor (NGF) is part of the _______ family

Answer 39

neurotrophin

Question 40

What are 4 pieces of evidence for the trophic function of NGF?

Answer 40

1. absence of NGF --> neuronal death 2. Increased NGF --> survival of excess neurons 3. presence and production of NGF in target cells 4. presence of NGF receptors in innervating nerve terminals

Question 41

What are three functions of neurotrophins?

Answer 41

1 survival of subset of neurons 2. # target cells contacted 3. # synapses formed

Question 42

Trk receptors and p75 receptor are _____ receptors

Answer 42

neurotrophin

Question 43

What are Trk receptors? What do they bind? What form of this molecule do they bind preferentially?

Answer 43

- receptor tyrosine kinases | - bind processed (cleaved) neurotrophins only

Question 44

What is p75 receptor activated by? For what molecule does it have a high affinity?

Answer 44

- activated by all neurotrophins | - high affinity for unprocessed neurotrophins

Question 45

What are the three cellular cascades which can occur from neurotrophin signaling?

Answer 45

- cell survival or death - growth or differentiation - stabilization or elimination of synapses - activity-dependent