Epithelial cells are organized into sheet-like structures and provide a selective and dynamic barrier between body compartments. The ability of epithelial cells to assemble into sheets is based on the coordinated polarization of groups of cells along a common vectorial axis. Epithelial cells polarize along an apical-basal axis, which involves the asymmetric segregation of cytoplasmic factors and plasma membrane domains, polarization of the cytoskeleton, and directional organelle transport, which collectively contribute to epithelial function and integrity. Loss of cell polarity is proposed to account for the malignant transformation of cancer cells, most of which arise from cells of epithelial origin.
Studies on Drosophila epithelia in various tissues have revealed a remarkably. consistent cell polarity programme that is established by evolutionarily conserved factors, including the partitioning defective (PAR), Crumbs (CRB), and Scribble (SCRIB) protein complexes, which mark distinct membrane domains to facilitate the formation of the apical-basal polarity axis. Examples of polarity mechanisms that do not rely on these key regulators have started to emerge, however, and it has become evident that different polarity pathways operate in a context dependent manner.
This proposal was aimed at elucidating polarity mechanisms in a new Drosophila epithelium, the adult gut. Peculiarly, the host laboratory has recently demonstrated that the conserved polarity regulators are entirely dispensable for epithelial polarity in the Drosophila midgut. Unlike any other cell type studied so far in Drosophila, polarity in the gut epithelium requires integrin signalling, which resembles the polarity mechanism commonly observed in mammalian cells. Hence, the gut epithelium may be a better model for mammalian epithelia than other insect epithelia, making it an attractive system in which to investigate polarity.
This proposal described the first large-scale analysis of polarity in the Drosophila adult midgut epithelium. The main aim was to conduct an in vivo forward genetic screen to identify novel epithelial polarity factors in the Drosophila midgut. As polarity in the gut is established in a different manner to all other well-characterized Drosophila epithelia, this project was expected to have a great potential to discover new polarity factors. Results from this study are expected to contribute to a better understanding of epithelial biology and will be of interest to many developmental biologists. Moreover, cell polarity is one among many biological processes that are deregulated in cancer, and polarity loss is proposed to be an event that is intricately connected to their malignant progression. By studying fundamental aspects of cell polarity establishment, this proposal has a potential to contributing to a better understanding of cancer biology.
