Function follows form: Linking epithelial polarity, growth control and morphogenesis in Drosophila

How do cells organize themselves internally, in order to take on a specific external form and function? Each of the >200 cell types in the human body has a distinct, sometimes radical architecture, yet how these properties arise from the relatively isotropic newborn cell remains largely unknown. We are exploring the biology of cell architecture in vivo by studying a simple cell type —epithelia— in a highly manipulable model organism ‐‐Drosophila. Using unbiased, large‐scale forward genetic screens as an entry point, we have identified novel molecular pathways that control cell biological features of epithelial organization, including apicobasal polarity. We have further investigated how this form ensures the proper functioning of cells during development, by influencing cell adhesion, signaling, and morphogenesis. A particularly dramatic and surprising case is seen in the Drosophila ‘neoplastic’ tumor suppressor genes, which simultaneously control both cell polarity and cell proliferation; mutation of these genes induces uncontrolled growth of disorganized cells that show several striking similarities to malignant human tumors. I will discuss insights that our work has provided into links between epithelial polarity, proliferation control, and organ morphogenesis.