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What are the stages of growth for a neuron?
cell body
Cell body and immature neurites
Growth cone differentiates from other neurites
Other neurites become dendrites and Growth cone become axon
Dendrites get spines and axon branches
Where are neurons made?
Ventricular zone
How does the neurons migrate?
Migrate over each other and crawl over each other to form layers of cerebral cortex - they migrate a large distance radially to pattern the cerebral cortex
What is important for neurons to function properly?
They must extend to reach the right target
What is the neural growth led by?
Only the actual axon has a growth cone - the leading process is when it is not yet an axon
How do growth cones grow?
Have very complicated cytoskeletal machinery. Tyrosinated and acetylated microtubules as well as lamellipodia
What can cause defects in neuronal migration?
Mutations in doublecortin (DCX)
What stops migration in a scratch assay?
Depolymerization of microtubules
What happens to cell migration when they are treated with colchicine?
They make several lamellipodia but there is no cell polarization
How do microtubules alter the activation state of Rho family GTPases?
Changing GEF and then shifting Rho into an active state, there must be something microtubules do to inhibit Rho
What happens when you get rid of microtubules in terms of cell growth?
You get stress fibers. You get stress fibers by making dominant active Rho. By treating them without Rho and take away the microtubules there are stress fibers from the absence of them
How do microtubules affect Rho family GTPases for movement?
Must activate Rac and inhibit Rho
What do pioneer microtubules do?
Penetrate into the lamalliodia and filopodia
What do microtubules sequester and inactivate?
A Rho-GEF. GEFH1 binds directly to the microtubules. All along the microtubuels there must be a Rho GEF which would give you Rho activation and then you get stress fibers.
When microtubule protrudes in to actin - it is generating actin. RTHey help with the polarization of the cell.
Without microtubules and actin - w/o microtubules, the actin just can’t polarize the cell
What is the phenotype fo DCX-KO iNeurons?
excessive branching
What happens for DCX-KO iNeurons for neuron migration?
Reduced migration and nuclear movements
What causes the restriction of microtubule movement?
Polyglutamylation, contributes to a way of specializing microtubules from the tubulin code
What are netrins?
Guidance cues - netrins can attract some growth cones and repel others
What are semaphorins?
Semaphorins just repel growth cones (variety of netrins)
What do mice lacking netrins show that is defective?
Defective spinal chord organization.
