Regulation of BMP signaling in the wing of Drosophila

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The ability of organisms to control signaling between cells is critical to the formation of precisely defined cell types, and to thereby control the size and patterns critical to the formation of tissues and organs during both embryonic development and adult life. Failures in the regulation of that signaling are known to underlie human birth defects and a variety of important health problems, including the excessive cell growth that causes cancers. One of the most important of the signals between cells is carried by a family of molecules termed Bone Morphogenetic Proteins (BMPs); in fact, the BMP signals are critical to the normal development of almost all animal species. However, the way in which BMP signaling is regulated is still poorly understood. This project involves a series of studies that will identify and characterize previously unknown regulators of BMP signaling. It uses for these studies the fruit fly, Drosophila melanogaster, since the genetic and molecular manipulations possible in this organism are unmatched by any other experimental system. The studies make use of a Drosophila tissue exquisitely sensitive to the loss of BMP signaling; the loss of this tissue in mutant flies provides a powerful method of identifying defects in novel members of the BMP signaling pathway. These studies have already led to the isolation and characterization of three novel proteins, now known to be shared by humans, that bind to and regulate BMP signals during their passage from cell to cell. The Broader Impacts of this project are several. It will used to advance discovery by training both graduate and undergraduate students; undergraduates are involved not only in senior-level independent study classes but also as part of the University of Winsconsin's introductory biology course. Many of these students have gone on to productive careers in the biosciences, as graduate students, postdocs or faculty. The project also aids in the promotion of underrepresented groups, and the majority of both graduate and undergraduates so trained have been women. The PI is also heavily involved in introductory and advanced undergraduate education, and presents the research findings to students as part of their introduction to scientific methodology. The molecular reagents and Drosophila strains developed in the lab are made available to other researchers either directly or via the national stock centers, and the award is used to support the PI's websites on techniques and genetic stocks. The PI has also has used this work to broaden interactions between the biological and mathematical communities through efforts to mathematically model the action of specific molecules.