Lecture 3 - Differentiation and Survival of Nerve Cells

Question 1

What is a major force driving later development of the brain?

Answer 1

proliferation of neural stem cells

Question 2

In the final week of the rat or mouse is not changing the morphology of the early embryonic brain but is rather?

Answer 2

populating the number of neurons and growing them tremendously and they proliferate from the subventricular zone

Question 3

What are the two different modes of division that neural progenitor cells?

Answer 3

symmetric and assymetric

Question 4

What happens in symmetric division of neural progenitor cells?

Answer 4

-one cell becomes two pluripotent cells

Question 5

What happens in asymmetric division of neural progenitor cells?

Answer 5

can get one neuron and glia or one neuron and one pluripotent cell

Question 6

Through which mode of division do neurons derive from and why?

Answer 6

assymetric because they value differentiation

Question 7

Through which mode of division do glia derive from and why?

Answer 7

symmetric division because they value proliferation

Question 8

Early experiments that took neural precursors and put them in a Petri dish and watch what happens over time in the absence of any different chemical or neural peptides and you will see that a single cell divides and you get a neuron or an oligodendrocytes and they reach terminal differentiation through staining or the machinery that make gaba or glutamate; when it becomes a glial precursor it will be an oligodendrocyte or astrocyte and once this fate is crossed cannot go back; neurons and glia come from ectodermal progenitor cells; glial cells generally keep dividing over time

Question 9

How does the initial migration of cells populate the early nervous system?

Answer 9

-radial glial cells serve as precursors to neurons in the CNS and provide a scaffold for radial neuronal migration in the brain

Question 10

How do neurons travel in the CNS via radial glia?

Answer 10

from the subventricular zone in the apical surface all the way out to the basal or pial surface

Question 11

During mitosis what do radial glial cells move along and then do what?

Answer 11

move along the apical/basal axis and then divide

Question 12

After division radial glial cells give rise to post-mitotic neurons that migrate away from the ventricular zone using radial glia as a guide how?

Answer 12

radial glia project a long sting rod and then its daughter cells gets into the hierarchy and moves itself to migrate out; radial glial cells in a neuronal precursor; usually used for excitatory neurons

Question 13

What intracellular signaling systems determine the fate of neurons vs. glia?

Answer 13

Delta acts as a ligand for notch and determines neuronal fate

Question 14

What are the four steps in delta notch signaling?

Answer 14

1. delta signaling will increase in the left cell due to extrinsic factors and bind to notch on the right cell
2. the intracellular domain of notch will be cleaved once delta is bound and enter the nucleus to suppress delta expression
3. less delta from the right so notch on the left will receive fewer delta signaling and will have more delta
4. high notch leads to glia and low notch leads to neuron

Question 15

What does notch signaling regulate?

Answer 15

the fate of cells in the developing cerebral cortex; whether a cell acquires a glial progenitor or neuronal progenitor cell fate

Question 16

In the presence of high notch a stem cell will become a glial progenitor cell if high notch persists what will the glial cell become?

Answer 16

astrocyte

Question 17

In the presence of high notch a stem cell will become a glial progenitor cell if low notch persists what will the glial cell become?

Answer 17

oligodendrocyte

Question 18

In the presence of low notch a stem cell will become a neuronal progenitor cell if low notch persists what will the neuronal cell become?

Answer 18

a neuron

Question 19

How is layered organization of the cerebral cortex established?

Answer 19

-migration terminates in the cortex and you will see an organized layer of neurons which have reached their terminal organization and will see very linear organized neuronal cell bodies

Question 20

Why do neurons migrate along radial glial cells to establish what?

Answer 20

the layered organization of the cerebral cortex

Question 21

How do the neurons migrate in the cerebral cortex to create a layered organization of the cortex?

Answer 21

-as the neurons approach the basal or pial surface they stop migration and detach from the radial glial cells and follow an inside-first outside-last pattern of migration leap frogging the previous neuron

Question 22

What does a defect in the reelin protein cause in cortical migration?

Answer 22

reelin is an ECM protein that attract the neurons so they can hop off at the appropriate time and create the layers - when not present it leads to the neurons riding up the scaffold the whole way through inverting the cortical layers

Question 23

What does a defect in the double cortin protein cause in cortical migration?

Answer 23

double cortin localizes to microtubules suggesting movement of nucleus along these microtubules is involved - leads to lissencephaly or smooth brain or lack of cortical folds - have developmental problems and seizures

Question 24

What helps neurons migrate along radial glial cells?

Answer 24

microtubule-associated motors - there are many genes that make up a protein scaffold that binds to the nucleus to move it since the cell body with the nucleus needs alot of skeletal structure to move but you need to constantly deconstruct and reconstruct it again when you are moving and migrating so it needs to be firm and flexible so the targets are the centrosome which give the nucleus strength

Question 25

How are microtubules attached to the centrosome?

Answer 25

by a series of proteins that are targets for disruption in neuronal migration disorders - can give rise to lissencephalic brain

Question 26

What do central neurons migrate along glial cells and axons to reach their final settling position?

Answer 26

Three modes

1. radial migration - central neurons move along radial glial cells (excitatory neurons)
2. tangential - central neurons use axonal tracts as their guide (inhibitory interneurons)
3. free migration - occurs in PNS without 1 or 2

Question 27

Where are interneurons generated and where do they migrate tangentially to the cerebral cortex?

Answer 27

ventral telencephalon migrates tangentially to the cerebral cortex

Question 28

What are the two sources cortical neurons come from?

Answer 28

excitatory neurons from the ventricular zone and inhibitory from the medial ganglionic eminence

Question 29

Why did tangential migration likely evolve?

Answer 29

as a way to increase complexity in the brain

Question 30

What occurs in the interneuron LGE to olfactory bulb migration?

Answer 30

LGE which is where we have adult neural stem cells but they are special cells which repopulate the nose for you sense of smell

Question 31

What happens in free migration of neural crest cells to the periphery?

Answer 31

BMP signaling turns on transcription factors which express ECM proteases which enable the cells to embark on their journey to the periphery

Question 32

What are the final settling positions of neural crest cells?

Answer 32

DRG (have cell bodies of sensory neurons)
Sympathetic ganglia (have cells bodies of sympathetic neurons)
Melanocytes (have cell bodies of skin pigments)
-adrenal medulla
-undergo terminal differentiation once reaching position in periphery