Chapter 12 Neural Development Flashcards
Why are homeodomain transcription factors not necessarily HOX genes? Because, in order to be a hox gene, the gene must lie in the
Hox cluster
The genes in vertebrates which set up different regions of neural precursors are orthologous to the genes which allow neural precursor set up in vertebrates.
While we use very similar systems to specify neural development, this means the system is likely conserved, though in our system the genes will appear on the dorsal region, while the drosophilia have a nervous system which is ventrally based.
Proneural clusters, let’s talk about them.
What is distinctive about a proneural cluster? These clusters are specified by activation genes, and DV patterning genes in drosophilia.
Only a single cell from the cells in proneural clusters will become progenitor nervous cell? How is this settled?
Lateral inhibition and an oldschool notch delta duel.
You see notch is a receptor, the honest kind. The kind which has a cleavable intracellular domain.
I am sure you know where this is going. Delta is a bit of bad boy, and more then that, delta is the right shape to fit into notch, or at least, part of delta is. Following attachment of delta to notch there will be some cleavage of the protein on the intracellular domain of the cell. The region cleaved from notch is a transcription factor and will inhibit specialization of the cell as a neural precursor, and it will inhibit the production of delta. With that cell producing less delta, its neighbor will produce even more, until it has inhibited all of its neighbors and is the only producer of delta signaling in the proneural cluster. Notch intracellular segment will bind with a mastermind coregulator often as not.
What is NeuroD, hint, it is similar to MyoD.
Activation of NeuroD does what? While it is the key transcription factor which specifies neural identity. It Determines the cell to have a neural identity.
What happens if you insert a truncated form of delta which can bind to but not activate, notch into drosophilia?
We will see many more nerve cells develop, the reason for this is that the cells will not be able to have their lateral inhibition in proneural clusters.
Ok. We had our arms race/lateral inhibition, cell fought it out, it was cool. What happens now?
Now we see that the chosen neuroblasts move into the embryo (literally move to the inside of it)
Let’s look at vertebrates, where are our sources of nerve tissue.
Neural tube: will become or CNS
Neural crest: peripheral nervous system
Ectodermal Placodes: these often become sensory neurons
The nervous system develops in both an axial and radial manner, explain.
I will…
Axial development:
The anterior portion of the neural tube, soon to become our dear brain, it does so by swelling, constricting, and folding in specific regions.
Ventricular region: is the inside of something.
Neurons are born in the ventricular region of the neural tube. The migrate outwards as they are born on glial cells. They will then migrate outwards, with the oldest neurons being located closest to the center, and the youngest neurons migrating the farthest.
Reeler mice have a mutation which prevents the active migration of nerve cells, instead cells are displaced from division. How will patterning fall?
1 6 5 4 3 2
Where 6 was the most recently created and 1 the oldest. What does this show.
The patterning of neural migration we saw in the reeler mouse show that the neurons are specified by birthday, not position. We know that positional placement is not important
Because we see that without active migration the position is reversed, if the a gradient was being used then reeler mice would not reel, because their cells would still be organized according to this gradient.
How is induction of neural types accomplished in the dorsal ventral gradient of the neural tube?
SHH is high in the ventral region and low in the dorsal region. This is also what we saw in the early embryo. This gradient of SHH throughout the neurons of the future spine will activate series of transcription factors, which will in turn, activate, particular genes, inhibit particular genes (which where on in the absence of SHH) or activate a particular gene and inhibit a ventrally expressed gene which was present in the absence of SHH.
Looking at his diagram, We can see dorsal regions tend to have genes activated and SHH activation of transcription factors appears to be always inhibiting dorsal genes and sometimes inhibiting and activating genes.
Neurons travel across well defined paths
They use growth cones, and can be attracted or repelled by a ligand (chemoattraction or chemorepulsion) or attached ECM ligand (contact attraction and contact repulsion).
