Final Report Summary - CEPODRO (Cell polarization in Drosophila)
Cell polarity is fundamental to many aspects of cell and developmental biology and it is implicated in differentiation, proliferation and morphogenesis in both unicellular and multicellular organisms. We are studying the mechanisms that regulate cell polarity during both asymmetric cell division and epithelial morphogenesis in Drosophila. To understand these fundamental processes, we are currently using two complementary approaches. Firstly, we are coupling genetic tools to state of the art time-lapse microscopy to genetically dissect the mechanisms of cortical cell polarization and mitotic spindle orientation. In this context we have deciphered the mechanisms of mitotic spindle orientation downstream of the Fz signalling pathway in both Drosophila and Zebrafish and understood the role of Huntingtin in mitotic spindle orientation (Segalen et al, 2010, Godin et al, 2010). We have also determined the mechanism of E-Cadherin endocytosis (Leibfried et al., 2009) and how new E-Cadherin adherens junction are formed upon cell division (Herszterg et al., 2013). In parallel we have initiated a genetic screen to identify novel regulators of cell polarization and identified interesting mutants compromising the organization of the epithelial tissue. The study of the PTEN gene has led to a better understanding of the mechanisms of junction elongation during cell rearrangements (Bardet et al., 2013). Secondly, to bridge the cellular description of cell polarization and the morphogenesis of the tissue, we have developed innovative interdisciplinary approaches aiming at quantifying the mechanical stress as well as the cell and tissue dynamics (Bonnet et al., 2012; Ishihara et al., 2013). In this context, we have estimated the mechanical stress during morphogenesis and we have deciphered the role of the tumor suppressor FAT pathway in the regulation of tissue morphogenesis (Bosveld et al., 2012). Since the mechanisms underlying cell polarization and morphogenesis are conserved throughout evolution, the proposed experiments will improve our understanding of these processes not only in Drosophila, but in all animals.