Neurogenesis

Question 1

How is production of neural cells regulated?

Answer 1

Spatially and temporally.

For example:

Spinal cord - Early born cells - Neurons

Spinal cord - Late born cells - Glial cells

Neurogenesis is a balance between differentiation and differentiation.

Question 2

Describe spatial control in the developing spinal cord

Answer 2

Ventral regiona produce motor neurons

(Dorsoventral patterning, Shh signalling)

Question 3

Describe temporal control in the developing spinal cord

Answer 3

Neural precursors are generated over a long period of time.

Progenitors generate neural cell types according to their location. In many parts of the CNS, type of neural cell generated also chenges over time.

Progenitors in these regions are therefore multipotent.

In the ventral spinal cord, progenitors first generate neurons, but later produce 2 types of glial cell. First oligodendrocytes and finally astrocytes.

Question 4

What is the general role of proneural genes?

Answer 4

Promoting neural committment. They control commitment to a neural fate

Question 5

What are proneural genes?

Answer 5

A group of transcription factors characterised by a protein motif called the basic helix-loop-helix (bHLH) domain.

Question 6

Where are proneural genes initially expressed?

Answer 6

In the ectoderm, where the proteins are present in descrete groups of cells called proneural clusters. Only cells in these clusters have neural competence.

Question 7

Give some examples of proneural genes

Answer 7

• Achaete
• Scute
• Atonal
• NB - all proneural genes have bHLH in the protein that they produce

Question 8

What is the process when a cluster of competent cells express proneural genes in the peripheral NS?

Answer 8

1. There is a proneural cluster
2. Each of the cells has the potential (competence) to become SOPs.
3. Cells compete to determine which one becomes neural.
4. A single cell attains this fate (dark green) and then inhibits the remainder of the cells by lateral inhibition.

Question 9

What does notch signalling do?

Answer 9

Down-regulates proneural genes

Question 10

What are neurons generated from in the vertebrate neural tube?

Answer 10

Progenitor cells called radial glia

Question 11

What are radial glial cells and what are their properties?

Answer 11

Neural stem cells which are defined by 2 properties:

• Multipotency - capable of producing progeny cells that can differentiate into a range of both neuronal and glial cell types.
• Self-renewal - whilst some of their progeny exit the cell cycle to differentiate.
• Radial gilal cells have a long process which spans the depth of the neural tube.
• Cell body in VZ
• Cell division occurs at apical surface
• Radial process provides a guide for migration

Question 12

Describe the role of Notch signalling in vertebrates

Answer 12

• Inhibition - although not permanent with inhibited cells taking on a different, non-neural fate.
• Instead, they are only temporarily inhibited and retain their competence as neural progenitors.
• Therefore, by preventing commitment Notch inhibition maintains the population of progenitor cells for further neurogenesis.

Question 13

How do cells know what to become?

Answer 13

• Extrinsic signals from the environment

OR

• Intrinsic signals - information from transcription factors expressed by progenitor cell due to regional patterning.
• Cell fate is largely determined by intrinsic factors

Question 14

Describe the balance between types of division with the aid of a diagram

Answer 14

Question 15

What do radial glial cells produce in the developing cortex?

Answer 15

Intermediate progenitor cells which further increases the number of neurons produced.

Question 16

Describe the role of the cell cycle

Answer 16

• The number of cells being prouced needs to be controlled via:
  
  • Length of the cell cycle
  • Number of cells that re-enter the cell cycle vs leave the cycle and differentiate
• Many transcription factors and cell cycle regulators are involved in this.
• The time of the cell cycle is limited, so if the divisions are slower, it doesn’t take longer, the cell just makes fewer divisions in the time, so it must be regulated

Question 17

How are the layers of the cortical plate laid down?

Answer 17

Deep layers of the cortical plate laid down first, then superficial layers.

Superficial cells migrate past the deep cells.

Question 18

How is fate of cortical neurons determined?

Answer 18

By the time at which they migrate into the cortex.

Prior to migration cells can respond to environmental cues.

Question 19

What happens to early born / late born cells in the cortex?

Answer 19

Early born cells will adopt later cell fates in an older cortex.

Late born cells cannot respond to environmental cues from a younger cortex.

So - cells which have gone past a certain point can make something from their stage or later, but once they’re past that stage they cannot go back.