Characterization of pak kinase function in drosophila oogenesis

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The Rho family of Ras-related small GTPases act as molecular switches, cycling between "on" and "off" states. They convey information into the cell and regulate cell shape and cell movement through proteins such as Pak. Epithelia are sheets of cells that include the skin and components of internal organs and are very important tissues in the development of animals. During the formation of epithelia, the Rho family and Pak help shape these tissues into their final configuration. Much of what is known about the Rho family and Pak has been come from studying cultured cells and relatively little is known about how these proteins operate in an intact organism. We are using the fruit fly Drosophila to genetically characterize the mechanisms by which Pak regulates epithelial development. Drosophila is a popular research organism due to the advanced techniques that have been developed for studying it, including very sophisticated genetic tools and the ability to do detailed imaging of events at the cellular level within the context of a whole animal. We have been looking at the follicular epithelium in the ovary, a typical epithelium that covers the developing egg. Using this system, we hope to gain insight into how Pak regulates three important processes in epithelial development. The first process is the regulation of cell adhesion, which is critical in determing how cells "stick" together to form tissues. The second is the regulation of epithelial cell shape through regulation of a contractile structure called the actomyosin cytoskeleton. Finally, we want to known how Pak regulates the proliferation of epithelial cells. Previous studies in other laboratories have identified various proteins regulating these three processes and we suspect that Pak interacts with these other poteins, perhaps by modifying their activity. We will use both genetics and biochemistry to address the relationship between Pak and these other regulators of epithelial development. This work will be of interest to developmental biologists and cell biologists, furthermore, improper development of epithelia is a cause of diverse birth defects, and our work may yield insight into what cell signaling pathways are defective in such disorders.