ECM AND CELL MIGRATION IN MULLERIAN DUCT REGRESSION

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The long-range goal of the present study is to elucidate the mechanisms involved in Mullerian duct regression using crocodilians as a model system. The Mullerian ducts, which are the embryonic oviducts, develop in vertebrates of both sexes and then regress in the male due to the actions of the testicular hormone, MIS (Mullerian inhibiting substance). In mammals, regression is characterized by dramatic changes in the extracellular matrix (ECM); and work in mammals, birds and crocodilians suggests that it involves dedifferentiation and migration of the ductal cells to other locations in the embryo. The proposed research will investigate how alterations in the ECM cause the changes associated with regression and whether fibroblast growth factor ( FGF) contributes to this process. Therefore, this study has the potential to make a significant contribution to the current understanding of some of the fundamental processes that characterize both normal tissue morphogenesis as well as malignancy. Three sets of experiments are planned. First, migration of the ductal cells in vivo will be confirmed since it has only been observed in vitro. Second, the role of specific ECM molecules such as laminin and fibronectin will be examined using immunohistochemistry to identify changes in these components before and during regression. In addition, ECM antibodies will be applied to the ducts in vitro to observe the effect of blocking cell binding to the ECM. This experiment will provide information about which ECM molecules are directly involved in promoting cell migration. Third, because basic fibroblast growth factor (bFGF) has been shown to induce mesoderm as well as to promote cell migration, and it is released from basement membranes following their degradation, its possible function as the inducer of epithelial transformation and migration during regression will be investigated using immunohistochemistry to identify when and where it is present. Antibodies to FGF also will be applied to the ducts in vitro to block its effects.