Drosophila Neurogenesis

Question 1

Neurogenesis in Drosophila

Answer 1

Similar to vertebrate neurogenesis, it was researched to compare to vertebrates
In vertebrates, neural tubes develop on dorsal side

Question 2

DV axis may be inverted in arthropods and vertebrates

Answer 2

First noticed G. Saint Hilaire, has idea arthropods might be inverted vertebrates or other way round
A bone morphogenetic protein (BMP) or decapentaplegic signal (Dpp) is important for patterning:
- Dorsal side in Drosophila
- Ventral side in Vertebrates
Although named differently the genes were discovered to be important defining different neural domains in Drosophila and similar roles in mouse (a mammal)

Question 3

Neurogenesis - proneural cluster

Answer 3

Not all cells in fly neuroectoderm become neurons, some remain ectodermal
Single Neuronal cells selected from group of equivalent cells - a proneural cluster
Process uses highly important patterning mechanism - lateral inhibition

Question 4

Lateral inhibition part 1

Answer 4

Achaete/Scute genes set up cluster called proneural genes
Notch/Delta signalling pathway ensures selection single cell out of cluster
Achaete Scute proteins promote Delta expression
Delta transmembrane ligand 7, can only influence neighbouring cells
Delta binds activates Notch receptor, but is small difference in delta expression
Strong Notch signal will downregulate A/S, as result small difference in A/S expression will become amplified
High and continuous A/S expression activates Neural genes in just one of the cells in the proneural cluster
The other cells (“losing cells”) revert back to epidermal fate

vsx1 - marker for particular type of interneuron, can stain zebrafish embryos for it

Question 5

Asymmetric cell division

Answer 5

Again process employed is interesting because also happens in different tissues and organisms - asymmetric cell division
Like lateral inhibition it is basic developmental principle
After selection neuroblast, that cell will drop down from epithelium into interior of embryo
All cells in drosophila epidermis have inherent polarity - Apico-Basal polarity
Neuroblasts “remember” this polarity
After selection Neuroblast, will generate number of Neuronal and Glial cells in stereotypic manner
“Memory” consist of localised protein complex Bazooka (=Par3 in mammals) is part of this
Protein complex directs localisation of proteins and certain RNAs on opposite side of cell, “Numb” is important part as it is basal side of cell
Complex also orients mitotic spindle, determines plane of division
Cell divides into a neuroblast (the upper side of the cell) and a ganglion mother cell (Numb part of the cell, bottom)
Neuroblast is a “stem cell” so will undergo further asymmetric divisions into more Nb and GMC
GMC will undergo only one more cell division into either neurons or glia

Similar processes and genes used to specify adult sensory neurons in drosophila

Question 6

Recap

Answer 6

Although the details may be different, the same basic principles apply in mammals and Drosophila with respect to neurogenesis. Many basic principles were first elucidated in Drosophila.
The D/V axis appears to have inverted when comparing Mammals to Arthropods
BMP/dpp signalling was already acting in our last common ancestor
Two important developmental mechanism that are at work during neuronal development are:
Lateral Inhibition- Delta and Notch ligand-receptor system
=>Selects one cell from a small cluster
Asymmetric cell division- Bazooka/Par3/Pins
=>Ensures that after a cell division, the resulting cells 2 take on different fates