Research On The Neuroepithelial Maintenance And Transition In The Optic Lobe Of Drosophila Brain

The proliferation and differentiation must be tighly modulated during the organgenesis in animal development. Drosophila optic lobe is an excellent model system to study this process. The optic lobe of Drosophila derieves from the neuroepithelia which invaginated during embryogenesis. The neuroepithelia conduct symmetric divison to expand the cell pool at the early larval stage, and then swith to neuroblasts, which conduct asymmetric division to produce a neuroblast and a ganglion mother cell. What controls the maintenace and transition of neuroepithelial cells is largely unknown. In the thesis, we find that two conserved pathways, JAK/STAT and Notch, are both necessary and sufficient for the maintenance of the neuroepthelia and suppression of the transition to neuroblasts.In the mutant of JAK/STAT pathway, neuroepthelial cells disintegrate and swith to neuroblasts precociously, leading to developmental defects in the lamina and medulla, two visual processing centers in the optic lobe, while ectopic activation of this pathway is sufficient to induce ectopic neuroepithelial cells and inhibit the transition from neuroepithelia to neuroblasts in the optic lobe. We identify that crumbs acts as a downstream effector of JAK/STAT pathway according to the genetic interaction. We also find that crumbs regulates the adherens junctions and spindle orientation of the neuroepithelial cells.In the loss of function mutant of Notch or its ligand Delta the neuroepithelial cells in the optic lobe do not expand but instead disintegrate while medulla neuroblasts are generated prematurely, which leads to premature neurogenesis in the medulla. Conversely, ectopic Notch pathway activation results in ectopic neuroepithelial cells; numb loss of function mimics ectopic Notch activation, suggesting that Numb may inhibit Notch signaling activity in the OPC neuroepithelial cells. Clonal analyses of loss-of-function alleles for the pathway components, including N, Dl, Su(H) and E(spl)-C indicate that the Delta/Notch/Su(H) pathway is required both for maintaining the integrity of the neuroepithelia in the optic lobe and for inhibiting medulla neuroblasts formation, while E(spl)-C is only required for the latter. We also identify that Notch is sufficient but not necessary for the neuroblast self-renew.