Binary Decisions

Question 1

What determines the fate of with neuron a progenitor cell will become?

Answer 1

• BMP, Wnt, Shh gradients converted to a GliA/GliR gradient and the induction of a specific set of transcription factors which act cell-autonomously to determine progenitor identity

Question 2

What happens as cells in the neural tube differentiate?

Answer 2

They move laterally, away from the ventricular zone and differentiate into mature neurons in the MANTLE ZONE

Question 3

What builds up the layers of the neural tube?

Answer 3

Cells migrating to the mantle zone, away from the ventricular zone and differentiating into neurons

Question 4

What happens to the neuroepithelial cells which don’t become neurons?

Answer 4

They remain at the ventricular zone and change shape into radial glia cells (neural stem cells)

Question 5

What do radial glia cells provide?

Answer 5

A progenitor pool of undifferentiated cells that are used to build up the nervous system over time in embryogenesis

Question 6

Where do glial cells sit in the neural tube

Answer 6

Their cell body sits at the VZ and their process extends to contact the outer surface of the forming neural tube

Question 7

What happens to the radial glial process as the neural tube gets thicker?

Answer 7

It gets longer

Question 8

What type of epithelium is the neural tube, before the daughter cells begin to migrate laterally?

Answer 8

Pseudostratified epithelium (looks like more than one cell thick)

Question 9

Why is the neural tube pseudostratified epithelium

Answer 9

The nucleus is able to undergo interkinetic migration, where the nucleus moves up and down the glial process, depending upon what stage of the cell cycle the nucleus is in

Question 10

Where is the nucleus in each stage of the cell cycle?

Answer 10

In G1/S - away from the lumen (starts to shuttle away in G1)

In M phase and cytokineses - nucleus is close to the lumen

Question 11

What happens to the glial cell during cytokinesis?

Answer 11

• Cell separates into 2 cells

- During this, the lateral attachment is lost and reforms in G1

Question 12

How can neuroepithelial cells divide?

Answer 12

1) Symmetrically to form 2 identical daughter cells - which are radial glial cells - expands the progenitor pool

2) Asymmetically to form 2 un-identical daughter cells
- A glial cell and a 2nd daughter which differentiate into a neuron

Question 13

How do neuroepithelial cells firstly divide and why?

Answer 13

Symmetrically to form 2 identical neuroepithelial cells which change shape to become radial glial cells

This expands the radial glia progenitor pool

Question 14

What determines if the division of the neuroepithelial cell will be asymmetric or symmetric?

Answer 14

Plane of division, as cytoplasmic of membrane components are asymmetrically located in the cell (polarised to one end)

This is determined through the Notch signalling pathway

Question 15

What occurs in a proneural mutant and why?

Answer 15

• No cells become neurons

- Due to mutations in Achaete and Schute

Question 16

What occurs in a neurogenic mutant and why?

What does this show/

Answer 16

• More cells become neurons
• Due to a mutation in Notch
• Shows that notch activity limits the amount of neurons that form

Question 17

What does notch regulate?

Answer 17

Lateral inhibition - preventing all cells from adopting the same fate (neurons)

Question 18

What is lateral inhibition?

Answer 18

• Transmission of inhibitory signal between a pair or cluster of cells, preventing the cells (which receive the signal) from adopting a particular fate

Question 19

Describe the process of notch signalling

Answer 19

1) Initially, all cells are equivalent (all cells are capable of adopting the same fate - they can make and respond to the inhibitory signal)
2) One cell upregulates Achete and Schute - upregulate Delta
3) Second cell receives more inhibitory signal - becomes inhibited
4) In cell 2, there is an increase in the Notch signalling pathway
5) Chain of transcription events - stabilise the change and prevent cell 2 from inhibiting cell 1

6) Upregulate supressor of HAIRLESS
7) Upregulates enhancer of SPLIT
8) Represses transcripton of Acheate-Schute
9) Prevents Delta from this cell

10) Cell 1 no longer receives Delta signalling - no activation of notch signalling - No repression of Acheate-Schute

Question 20

What is notch?

Answer 20

A receptor for the DELTA LIGAND

Question 21

How is delta maintained?

Answer 21

By TFs Acheate and Schute

Question 22

Which cell in the proneural cluster becomes the neuron?

Answer 22

The cell which has Acheate-Schute signalling and is therefore releasing Delta

(No notch signalling, no Delta received on its surface)

Question 23

When a single cell divides into 2 cells, what 3 decisions must the daughter cells have to decide on fate?

What determines these bilateral decisions?

Answer 23

1) Stay dividing or differentiate
2) Roof plate or neural crest cell
3) Become a neuron or oligodendrocyte

Notch signalling

Question 24

What signalling determines decisions during bilateral division?

Answer 24

Notch signalling

Question 25

What dictates later differentiation?

Answer 25

The transcription factor code in progenitor cells, which are determined autonomously by GliA/GliR

Question 26

What is the primary fate of notch signalling?

Answer 26

Neurons

Question 27

What determines the progenitor identity?

Answer 27

The set of transcription factors expressed