Notch signalling is a key pathway which has numerous roles in development. The canonical Notch pathway is ligand-activated and involves Notch receptor cleavage at the cell surface, releasing a transcription activating intracellular domain. The E3 ubiquitin-ligase Deltex (D?,-) has been proposed to mediate an alternative Notch activation mechanism, which is li~and-independent, and requires endocytosis of the full-length Notch receptor from the cell surface. This study shows that Dx, along with intracellular trafficking mutants, are required in the Drosophila ovary to ensure proper egg formation. The ovary consists of strings of egg chambers, each of which are the product of two stem cell populations, the germline stem cells and the somatic stem cells. These produce a germline cyst from which the oocyte develops, and a somatic follicle cell layer surrounding the germline cyst which controls the correct development of the egg chamber. Notch signalling is required in the germline stem cell niche and for correct specification of the follicle cells. dx and the trafficking mutant car, show defects in the somatic stem cell lineage which results in incorrectly packaged egg chambers. This results in a reduced fecundity and phenocopies loss ofNotch function. Using Notch reporters, I demonstrate that dx and car downregulate Notch signalling in various cell types in the ovary. Additionally, I show that Dx is intrinsically required for germline and somatic stem cell maintenance. This implies a novel cell autonomous role for Notch in both these stem cell populations. Stem cells are required in many tissues for their regeneration. An age-dependent loss of Notch signalling has previously been reported in mammals (Conboy et aI. 2003). In this study I demonstrate that Notch signalling is downregulated in the ovary as flies age, correlating with a decrease in egg chamber production. Furthermore, aged wild-type egg chambers show similar defects to those of young dx mutants. dx mutant flies also show reduced longevity with an average lifespan half that of wildtype flies. This suggests that a systemic decrease in Notch signalling throughout the body contributes to the ageing process.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:491480 |
| Date | January 2008 |
| Creators | Hung, Yvonne Hue Yee |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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