Lecture 8 - Neurogenesis

Question 1

When does neurogenesis occur in flies?

Answer 1

Post gastrulation

Question 2

What are the features of proneural genes?

Answer 2

• code for basic helix-loop-helix transcription factors
• drive the process of neural differentiation
• achaete-scute is expressed in groups of cells in the ectoderm known as pro-neural clusters
• only cells of the proneural clusters are competent to form neuroblasts and SOPs (sense organ precursors)

Question 3

What phenotype is shown by proneural gene mutants?

Answer 3

loss of function achaete scute mutants leads to loss of nerual precursors and neurons
-e.g. sensory bristles (derived from SOPs)

ectopic expression of acaete-scute results in extra bristles

Question 4

How are the cells that will form SOPs and neuroblasts selected?

Answer 4

• only one cell from each proneural cluster necaomes a neural precursor (SOP or neuroblast)
• leteral inhibition blocks the ability of other cells in the proneural cluster to become neural precursors
• good for producing evenly spaced cells of a particular lineage
  1. cells initially express high levels of proneural gene
  2. One cell is picked to express proneural gene (because it is able to supress the expression of proneural gene in the surrounding cells whilst maintaining it own high expression
  3. the other cells’ expression levels drop off (they lose completency)

Question 5

What are the function of loss of function mutations in neurogenic genes?

Answer 5

Normal function of the neurogenic genes is to inhibit specification of neural precursors

• Loss of function mutations lead to extra neuronal differentiation
• extra sensory bristles

Question 6

What signalling does lateral inhibition involve?

Answer 6

Notch-delta signalling

Question 7

What is notch?

Answer 7

Notch is a membrane bound cell surface receptor

-lateral inhibition

Question 8

What is delta?

Answer 8

Delta is a membrane bound-ligand that bind to the notch receptor
-lateral inhibition

Question 9

What are the features of Notch delta signalling involved in lateral inhibition?

Answer 9

Delta signalling via the notch receptor requires close association between the signalling and the recieveing cell

• signals via juxtacrine signalling
• delta does not signal to notch in an autocrine fashion (some cells express delta and notch - but this cannot signal back to itself)
• level of signalling recieved by the cell is dependent on the occupancy of many cell receptors

Question 10

What are the juxtacine signalling-regulatory interactions in volved in lateral inhibition?

Answer 10

• Proneural transcription factors, expressed in all cells of the proneural clusters activate and lead to the expression of delta, which is then expressed at the cell surface
• Activation of notch signalling by delta (once the delta ligand binds to the notch receptor) this leads to repression of the transcription of proneural genes, and consequently of delta

Proneural genes activate delta, detla activates notch in an adjacent cell, notch represses proneural genes which repress delta

Question 11

What are the processes of mutual inhibition verses lateral inhibition in the selection of SOPs and neuroblasts?

Answer 11

Initially notch-delta signalling results in Mutual inhibition
-balance between notch/delta signalling and proneural gene expression
-mutual inhibition maintains competence to form neural precursors because proneural genes continues to be expressed in all cells of the proneural cluster
Lateral Inhibition
-one cell eventually has a higher level of proneural gene expression
-high proneural gene expression leads to higher delta expression in that cell
-higher delta expression leads to an inhibition of the proneural gene expression in adjacent cells via notch
-instability allows lateral inhibition in surrounding cells
-

Question 12

What does lateral inhibition result in?

Answer 12

regularly spaced array of cell types

Question 13

What are the features of neurogenesis in the amphibian primary nervous system?

Answer 13

• not all cells in the neural plate differentiate into post-mitotic neruons in the primary nervous system
• non-differentiating cells remain as proliferative progenitors which differentiate in later pahses of neurogenesis

Question 14

How are cells chosen to differentiate into the primary nervous system in Amphibians?

Answer 14

Similar set of proneural genes to those found in drosophila, but are more complex

• multiple bHLH genes related to the drosophila proneural genes are present in amphibians
• many of which are expressed in the neural plate
  e. g. Ngn1, Ngn2, Ngn3 (expressed and correspond to differentiating columns of neurons, contain redundancy)

Question 15

What are the neuronic genes present in the amphibian primary nervous system?

Answer 15

• multiple notch related receptors are present and expressed in the neural plate
• multiple delta-related ligands are present and expressed in the neural plate (insitu hybridisation)

Question 16

What does overexpression of proneural genes in Amphibians result in?

Answer 16

-proneural gene overexpression leads to ectopic neuron formation
-similar activity and fucntion to the dorosphila embryo
SHOWN
-take mRNA coding for the genes and inject it into an embryo, this is translated and expressed
-proteins are stained with neural marker which higlights neurons in the brain and spinal cord

Question 17

What does overexpression of activated notch receptors in Amphibians results in?

Answer 17

inhibits the neuronal differentiation and maintains progenitor proliferation

Question 18

What conserved features are there of neurogensis?

Answer 18

• the basic mechanisms of neurogenesis are conserved in flies and vertbrates
• proneural and neurogenic genes have similar function in both animal groups
• the activity of proneural and neurogenic genes selects individual cells for differentiation into neurons

Question 19

What is the process of neurulation?

Answer 19

Neurulation is the physical process of neural tube formation

• during the process of neurulation the dorsal ectoderm or neural plate rolls up to form the hollow dorsal neural tube
• as a result of neurulation the tube is internalised