Notch signalling is a cell cell communication mechanism involved in many developmental decisions and diseases, including cancers across metazoans. Activation of Notch by its ligands, results in the release of the Notch intracellular domain (NICD), which enters the nucleus and regulates transcription. In many lineages Notch is activated iteratively, with different outcomes at each stage. On each signalling event, different target genes are activated but relatively few have been characterized and little is known about the mechanisms switching the response. Stem cells (SCs) in D. melanogaster exist in many tissues from embryogenesis to adult life and undergo asymmetric cell divisions to self renew and produce all differentiated progeny necessary in each particular tissue. Within many of these lineages, either the stem cell (e.g embryonic/larval neuroblasts, adult muscle progenitors) or their differentiated progeny (e.g neurons in the brain or enterblasts in the gut) receive Notch signals with different consequences. Aberrant Notch signalling in some of these lineages leads to the formation of hyperplasias (e.g larval neuroblasts). My goal is to investigate the extent to which the cohort of Notch target genes differs in various stem cell populations, during different time windows of normal or pathological development and elucidate the mechanisms that bring about these differences.
Zacharioudaki E, Housden BE, Garinis G, Stojnic R, Delidakis C, Bray SJ, (2016), Genes implicated in stem cell identity and temporal programme are directly targeted by Notch in neuroblast tumours, Development, Jan 15;143(2):219-31
Zacharioudaki E, Bray SJ, (2014), Tools and methods for studying Notch signaling in Drosophila melanogaster, Methods, Jun 15;68(1):173-82
Zacharioudaki E, Magadi SS, Delidakis C, (2012), bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation, Development, Apr;139(7):1258-69