Lecture 8 - neural crest cells and axonal pathfinding

Vesicles of the brain

There are two main vesicles, primary and secondary, there are 3 types of primary vesicles the forebrain, midbrain, and hindbrain. Those primary vesicles can be further divided into secondary vesicles in which there are 5.

What are the 5 main things neural crest cells can become?

1. PNS: neurons and axons beyond the spinal cord

2. Endocrine derivatives

3. Pigment cells

4. Facial cartilage and bones

5. Connective tissue

What type of stem cells are neural crest cells?

Multipotent stem cells, because they cannot give rise to the entire embryo

What are the four main anatomical regions neural crest can be divided into

1. Cranial/ cephalic: gives rise to bone, cartilage, neurons, pigment cells, connective tissue of the face

2. Cardiac: muscular-connective tissue of arteries and the septum

3. trunk: makes sympathetic ganglia, pigment cells, and adrenal medulla

4. Vagal/sacral: parasympathetic nerves of the gut

Development of neural crest cells

Their differentiation becomes more restricted as they develop, the first bunch can become four different types of neural crest cells but the more the divide the more specified they become (can become less things)

Delamination of neural crest cells

Leaving of the neural tube, this occurs due the loss/down regulation of adhesion molecules, which is facilitated by Sox2 inhibiting Snail2 which inhibits both N and 6B cadherins

Contact inhibition

This is when if the migrating neural crest cells run into each other they will establish a contact surface and then migrate away from that surface, ensuring no backwards migration and that the cells are dispersed

Collective migration

Occurs due to the cells exerting forces on one another (in a particular direction), they are able to move as a group due to both contact inhibition and co-attraction between cells. Cells in the leading edge produce protrusion that guide and drive movements.

Migration pathways

There are 2 migrating pathways, ventral and dorsolateral. The ventral pathways is the early migrate cells and they differentiate into sensory and autonomic neurons. The dorsal pathway is the late migrating cells and they become melanocytes and melanin pigment cells

Ephrin

A guiding molecule for the migration of the neural crest cells, wherever ephrin is present the neural crest cells will not be, except for the melanocyte lineage of crest cells (dorsolateral migrating through the skin) who are found wherever ephrin is

Cranial neural crest cell migration

Their migration is more of a chase and run scenario, placoid cells guide the neural crest cells using a gradient of chemoattractant (SDF1), they use the CXCR receptor for SDF1 to sense attraction and direct migration towards themselves, once the neural crest cells meet up to them they use contact inhibition to allow the placode cells the push themselves and move away from the neural crest cells

Neural connections

Functional connections with surrounding neurons is possible due to axons and dendrites

growth cone

movement apparatus of the axon

Making the axon connections

Growth cone migrates nad senses the environment, elongation and contraction allows it to migrate, the parts it is elongating and contracting are microspikes which fan out in front of the growth cone sampling the environment and sending signals back to the cell body. Depending on the guidance molecules in the environment the axon slowly finds its way to the appropriate target

Elongation of growth cone

Elongation is facilitated by actin polymerization, when it needs to get longer more actin forms polymers, and when it needs to contract it moves actin polymers

Guidance cues

The cues fall into 4 protein families, ephrins, semaphorins, netrins, and Slit proteins. Depending on type and time of signal determines if it is an attractive or repulsive signal

Pathway selection

The axon travels along a route that leads them to a particular region

Target selection

Once in the correct area the axon recognizes and binds o a set of cells and form a stable connection

Address selection

After selecting a few cells the axon decides to establish with them, they select one to have a strong connection with out of all the possible targets

Synapse formation

This is a specialized junction where an axon contacts its target cell, happens in several steps

1. Growth cone makes contact with target cell, no specializations in either membrane

2. Ach receptors begin to cluster at the surface where the axon has made contact

3. Axon terminal fills with vesicles containing neurotransmitters, the cell it made contact with ECM produces B-laminin that binds to the growth cone acting as a stop signal

Competition between synapses

Multiple axons can arrive at the same cell and compete for binding, but once a motor neuron is active it suppresses the synapses of the other neurons, the less active synapses are eliminated