The goal of this investigation is to understand the mechanisms by which growth factors contribute to the embryonic development of Drosophila. Growth factors are important modulators of cell growth and differentiation in all higher organisms but their roles in development are not well understood. A better understanding of growth factor functions will be important for appreciating their roles in disease and for learning to manipulate them for the purpose of perturbing cell growth in the treatment of diseased or wounded tissue. The availability of mutations in Drosophila and detailed methodologies with which to study Drosophila embryonic phenotypes provide significant experimental advantages for investigating the roles of growth factors in development. Although there is an extensive body of knowledge about the genes involved in pattern formation and determination of cell fate in Drosophila, the role of Drosophila growth factors in these processes is largely unexplored. The Drosophila gene decapentaplegic (dpp) encodes a protein whose sequence and biochemical properties are similar to growth factors in the transforming growth factor Beta (TGF-Beta) family. Members of this family have diverse functions including the regulation of cell proliferation, terminal differentiation, deposition of bone, secretion of follicle-stimulating hormone, and mesoderm induction. In Drosophila the dpp protein is required for normal gastrulation, organogenesis of specific tissues, and pattern formation along the dorsal/ventral axis of the embryo. The role of dpp in specific places and times during embryogenesis will be investigated by examining the behavior and developmental fate of cells in mutant embryos. To understand how dpp affects cells, genes that respond to dpp will be identified by screening available probes and by identifying new genes from subtraction libraries. The importance of these genes to dpp's embryonic functions will be determined by generating mutations in the genes and characterizing the phenotypic effects of the mutations on embryogenesis. Using the polymerase chain reaction, thorough screens will be carried out to identify other Drosophila growth factor genes in the TGF-Beta or heparin-binding growth factor families. This approach has recently identified a new Drosophila gene homologous to the murine VgR-1 growth factor of the TGF-Beta family. Newly identified Drosophila growth factor genes will be subjected to molecular and genetic analyses similar to those carried out or in progress for dpp with the goal of defining the molecular interactions through which each growth factor affects development.
