Rapidly accumulating evidence has demonstrated that several oncogenes are constituents of pathways for the transduction of signals for growth and differentiation. The EGF receptor (the erbB oncogene) belongs to this category. Little is known about the function of the receptor in the context of the entire pathway or in the context of development and differentiation of a whole organism. Such knowledge is invaluable for a broader understanding of malignant transformation and for diagnosis and therapy of cancer, especially since various oncogenes may function in different levels of the same pathway. A Drosophila gene homologous to the human EGF receptor gene has been isolated and sequenced. It shows a high degree of homology to both extracellular and intracellular domains of the human protein. Since the functions of the human and Drosophila proteins appear to be analogous, this proposal is aimed at the utilization of Drosophila genetics and biology to study the function of the gene in the context of the whole organism. Mutations in the resident gene will be isolated, and their developmental effects analysed. The mutations will be used in conjunction with mosaic analysis to determine the periods and tissues in which the protein is required during development. The genetic results will be corroberated by in situ hybridization of a probe prepared from the receptor gene to thin tissue sections of Drosophila embryos or larvae. An additional copy of the cloned gene joined to the inducible HSP70 heat shock promoter will be introduced into the germ line. Effects of overexpression of an intact or altered coding region of the gene can then be analysed. Any visible mutant or lethal effects of such manipulations can be used for isolation of dominant suppressor mutations coding for proteins that interact with the receptor or regulate it.
