Functional genomic analysis of morphogenesis

Abstract

Changes in cell shape are central to development and disease. To systematically dissect the temporal‐spatial control of cellular processes in morphogenetic programs, we are applying functional genomic and in vivo genetic approaches in Drosophila. Specifically, we are investigating developmental mechanisms that spatially regulate specific lipid signals that mediate cellular elongation and underlie human diseases. The localized regulation of interrelated but distinct forms of phosphoinositide phosphates (PIPs) serve as nodes that spatially coordinate cellular functions through the recruitment of proteins to discrete membrane compartments. We are employing systematic RNAi screens for genetic modifiers of specific cell‐based phenotypes to help identify molecular mediators of phosphoinositide signaling pathway function. We are also investigating subcellular localizations of different PIPs in live cells undergoing cell shape changes using a collection of fluorescently‐tagged PIP‐binding proteins and microscopy imaging. The combination of RNAi loss of function and imaging approaches have helped us to identify specific roles for individual members of large conserved families of phosphoinositide regulators, as well as to delineate the functional significance of specific PIP pools important for cellular elongation.