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CAMSAP 1 is a spectrin associated, Calmodulin regulated protein that is a member of a large ubiquitous family of cytoskeletal proteins, defined by a novel C-terminal domain, the CKK domain. The CAMSAP family member in the fruit fly Drosophila melanogastor is encoded by the gene short spindles4 (ssp4). Little is known about this gene but a role in microtubule dynamics has been shown in cultured cells. I have interrogated bioinformatics databases and compared Ssp4 with Human CAMSAP proteins and found many similarities, and some differences, between them. Using in situ hybridisation I show that ssp4 transcripts are expressed in the gut, head and central nervous system during embryogenesis. An antibody that recognises the Ssp4 C-terminus reveals expression throughout the embryonic development of the gut and nervous system, and in a discrete population of cells in the head. I have investigated the effects of two independent P-element induced mutant alleles of ssp4 and show that mutant flies die in late embryonic or early larval stages. Disruptions to the locus do not seem to affect the nervous system but mutants were found to have aberrant head involution. I present preliminary evidence that suggests this defect may be the result of reduced apoptosis in the embryo. Head involution is a complex process, dependent upon co-ordinated changes to cell shape and the movement of groups of cells from different origins. As Ssp4 is a multi-domain cytoskeletal protein that is required for embryonic development, it may play a role in processes that are common to these morphogenetic events.

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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.

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