Real-time analysis of the dynamics of coordinated epithelial plasticity. Lara C. Skwarek, David Bilder. Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA.

   During development, morphogenetic rearrangements often result from regulated changes in both individual and collective cell behavior. One such example is the remarkable cellular transformation known as epithelial-mesenchymal transition (EMT). During EMT, epithelial cells dramatically alter polarity, change shape and acquire mesenchymal characteristics, often without cell division. Such programs of cellular plasticity are essential for normal development and are also hallmarks of tumor metastasis. Strikingly, we still lack a comprehensive knowledge of the integrated mechanisms involved in coordinating such plasticity in vivo, leaving a large gap in our understanding of these important cellular events during both development and disease. To address this I have been studying the final steps of wing development, during which a bilayered epithelium comprising the immature wing disassembles, allowing for rapid maturation of the adult wing. Though this process differs from classical EMT events, it nevertheless requires coordination of the disassembly and ultimate death of an epithelium with secretion of components required for wing maturation. Using a combination of high resolution live imaging and genetic manipulation I have observed that regulated loss of E-cadherin and adherens junction components precedes dramatic shape changes within the epithelium. In addition, preliminary results indicate that knocking-down known regulators of plasticity with RNA interference causes defects in wing maturation. This system is particularly suited for studying the early stages of epithelial cell transition, and together with an unbiased forward genetic screen, these studies will identify new mechanisms regulating the cell biology of epithelial transition and cellular plasticity.