During animal development, growth and patterning must be intimately coordinated to generate organs of reproducible size and shape. Compared to our relatively comprehensive understanding of the mechanisms governing pattern formation, much less is known about how the size of an organ is controlled. We are using the adult organs of Drosophila, in particular the compound eye, as a model to study size- control mechanisms in development. One gene that regulates organ size is dPTEN, a Drosophila homolog of the human PTEN tumor suppressor gene, which encodes a protein with both protein and lipid phosphatase activities. dPTEN regulates both cell growth and cell proliferation, and loss-of-function mutations of dPTEN result in enlarged organs with increased cell size and cell number. However, it remains to be determined how dPTEN coordinately controls both cell growth and proliferation. To further elucidate the function of dPTEN in size control, we propose three specific aims. First, we will examine how dPTEN interacts with other growth regulatory genes. We will use antibodies to determine if dPTEN co-localizes and co-precipitates with other known growth regulatory proteins. Second, we will study how different domains of dPTEN contribute to its biological function by generating site- directed mutations in dPTEN and assaying their activities in vivo. Third, we will carry out genetic and protein-interaction screens to isolate factors that function together with dPTEN in control of organ size. Understanding the molecular mechanisms of dPTEN function will not only provide insights into size control mechanisms in development, but also shed light on how PTEN functions as a tumor suppressor gene in humans.
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