Notch signalling, a cell communication pathway conserved throughout the animal kingdom, is involved in many developmental processes and linked to many diseases including cancers. While Notch signalling is well known for its function in cell fate control, it has also been implicated in regulating cytoskeleton and cell morphology. For example, Notch is required in Drosophila for the formation of an actin-myosin fence between dorsal and ventral compartments in the wing, for the migration of border cells in the ovary and for correct axon connectivity in the nervous system. However, although the regulation of cell architecture and behaviour is a key process during morphogenesis and tissue formation, it is unclear how Notch exerts its effects on these processes. The aim of this proposal is to identify and analyse new Notch target genes involved in cell architecture regulation. Amongst direct Notch targets identified through genome-wide expression array and chromatin immunoprecipitation are a cohort of genes implicated in cytoarchitecture regulation. Using a combination of genetic approaches, I intend to investigate the function of these novel genes in wing disc formation, border cell migration and axon pathfinding to elucidate their contribution to these morphogenetic processes regulated by Notch. In addition, biochemical, molecular and cellular analyses will be used to assess their functions. Through these approaches I aim to determine which genes play a role in directly transducing the consequences of Notch activation into changes in cell behaviours. Discovering genes that mediate effects of Notch on cell architecture should provide new insights not only for the understanding of Notch function in development but also for the understanding of tissue morphogenesis in general. Besides, given the importance of both Notch signalling and cell organisation integrity in many cancers these new identified factors might be of particular importance in therapeutic research.
Field of science
- /social sciences/sociology/social problems/migration
- /medical and health sciences/clinical medicine/oncology/cancer
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