The regulation of early embryo cleavage by cell polarity proteins

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Genome sequencing has identified the proteins required for making an animal. However, we are just beginning to understand how these proteins function together to build animal tissues. The most common tissues in the body are the sheets of cells that form our skin and organs. How do proteins organize these sheets to form the skin, lungs, heart or stomach? My lab is addressing this fundamental question using the fruit fly as a simple, tractable model system. We can use the powerful genetic techniques available in the fruit fly to disrupt protein function and to identify proteins important for tissue development. We couple these manipulations with advanced imaging techniques to monitor molecular positioning, cell shapes and interactions, and tissue organization as an animal embryo develops. In this way, we are discovering the proteins and molecular networks that direct specific changes in tissue structure for animal development. By linking sets of proteins to specific tissue changes, the molecular bases of tissue changes will be defined, and thus the links between the genome and the whole animal will become clear. The same proteins and cellular processes underlie tissue development across animals. Thus, our research in the experimentally advantageous fruit fly embryo is important for understanding how human tissues form normally, and for understanding how they break down in diseases like cancer. It is also relevant to the engineering of tissues and organs. This proposal focuses on how the first tissue of a developing animal is generated through early embryo cleavage (cell division). At the molecular and cellular level, we are pursuing how proteins that form spatial landmarks in the cell (polarity proteins; the kinases Par-1 and aPKC) regulate the positioning and contractility of networks of cables and motors (actomyosin cytoskeleton networks) to divide the cell at the correct location, and to continue doing so with many rounds of rapid division. We are studying conserved proteins and taking advantage of unique aspects of early fruit fly development to identify cell division regulatory mechanisms that may have eluded detection in other model systems. Our research should be generally relevant to cell division across animals.