L3: Axonal Growth/Tropism

Question 1

What is the first event that gives neural cell identity?

Answer 1

Polarization (when an axon is formed)

Question 2

What are growth cones?

Answer 2

They are specialized motile structure located at the tips of axons which will respond to guidance molecules to help direct where axons should form connections. They are made of lamellapodium (actin and microtubule) and filopodia (actin)

Question 3

List the 3 main functions of growth cones

Answer 3

1-explores ECM
2-determines direction of growth
3-guides extension of axon

Question 4

T/F: Growth cone shape changes at “decision points” which is impt in making connections

Answer 4

True

Question 5

What are the 2 big groups of axon guidance molecules

Answer 5

1 - non-diffusable (contact-attraction; contact-repulsion)

2 - diffusable (chemoattraction; chemorepulsion)

Question 6

List the 5 non-diffusable axon guidance molecules and state whether they are attractive and repulsive

Answer 6

1) ECM - collagen, laminin, fibronectin in PNS = contact attraction
2) Cell adhesion molecules (CAM) = contact attraction = Ca2+ independent homophilic interactions
3) Cadherins = contact attraction = Ca2+ dependent homophilic interactions
4) Semaphorins = contact repulsion
5) Ephrins = contact repulsion ** bidirectional signaler

Question 7

What are the 2 diffusable axon guidance molecules and state whether they are chemoattractive or chemorepulsive

Answer 7

1) netrins
- repulsive = UNC family receptors on growth cones
- attractive = DCC family receptorson growth cones
2) Slit
- repulsive = ROBO receptors

Question 8

Midline is formed at gastrulation. What are some obstacles that are presented to cells at this midline?

Answer 8

1 - cells have to avoid target cells on same side of spinal cord
2 - cells have to cross at a very specific site in cord
3 - once crossed, cannot recross
4 - cells have to find target cells on other side of cord

Question 9

there are some obstacles presented to cells at midline that need to cross the cord. What molecules help in overcoming these problems?

Answer 9

Netrin & slit

• commissural axons express DCC -attractive for netrin
• netrin guides commissural axons to cross.
• once crossed, these axons upregulate ROBO, slit in midline will prevent recrossing

Question 10

What’s the relationship btw ROBO & DCC receptor expressions on growth cones?

Answer 10

ROBO signaling inhibits DCC, vice versa

Question 11

Synaptogenesis in NMJ involves motor axon making contact with a muscle fiber. After contact, the nerve will become motor terminal and muscle will become post-synaptic terminal. Which molecules are in play to induce muscle differentiation into post-synaptic terminal?

Answer 11

agrin induces muscle into post-synaptic apparatus; will activate MuSK increasing ACH receptors

Question 12

Synaptogenesis in superior cervical ganglion -how do axons know to synapse at correct targets even though they synapse at the same location?

Answer 12

“correct” pre- and post-ganglionic neurons have higher affinity for one another

Question 13

Synaptogenesis in CNS involves? Role of neurexin & neuroligin?

Answer 13

• cadherins & protocadherins = 1st step
• neurexin: localize cytoskeletal elements, Ca2+ channels to pre-synaptic membrane
• neuroligin: recruits NT receptors & proteins to post-synaptic membranes

Question 14

After neurons make synaptic connections, what are they dependent on for survival?

Answer 14

the post-terminal apparatus secretes neurotrophins & neurons will compete for these neurotrophins for survival

Question 15

Does synaptic rearrangement happen during post-natal life?

Answer 15

Yes, it rearranges constantly thru out life and competes for neurotrophic signals
Example:
1 -initially, skeletal muscle fibers innervated by multiple neurons (polyneural innervation0
2 -synaptic inputs are eliminated until only one neuron remains

Question 16

What are the functions of neurotrophins? List some of the neurotrophins

Answer 16

1 - survival of select neurons
2 - formation & maintenance of appropriate # of connections
3 - refining axonal branch patterns

Nerve growth factor (NGF), BDNF, NT-3, NT-4/5

Question 17

What happens when there is no nerve growth factor (NGF)?

Answer 17

neuronal death

Question 18

What happens when there’s increase NGF?

Answer 18

survival of excess neurons

Question 19

T/F: Different neurons react the same to different neurotrophins

Answer 19

False; different neurons react differently to different neurotrophins

Question 20

List the 2 family of neurotrophin receptors on the nerve/motor axon? These neurotrophin receptors have different affinities for different neurotrophins.

Answer 20

1) Trk receptors (receptor tyrosine kinases)
- Trk A –> NGF
- Trk B –> BDNF, NT-4/5, NT-3
- Trk C –> NT-3
* *high affinity for processed (short) neurotrophins
* *cell survival, activity dependent plasticity

2) p75 recetpr
- can be activated by all neurotrophins
* *high affinity for long neurotrophins
* *axon w/o trk receptors, only p75 = cell apoptosis

Question 21

What does it mean that neurotrophin + receptor binding is selective not only in terms of class of neurotrophins but length of neurotrophins?

Answer 21

The 2 classes of receptors (Trk & p75 receptor) bind to different neurotrophins. They also have specific affinity for different lengths (processed or not) of neurotrophins.

Question 22

Which class of axon guidance molecules plays a role in fasiciculation?

Answer 22

Cell adhesion molecules (CAM)