The Drosophila EGF receptor (EGFR) is required for a number of developmental processes involving distinct cell responses. Receptor activity is governed by four agonists including Spitz and Vein. The ligands may be deployed for particular developmental events because they induce a certain strength or duration of signaling and hence elicit the desired cell response. Individual and comparative analysis of the ligands will be required to develop this idea. The focus of this proposal is analysis of the neuregulin-like ligand, Vein, and a comparison of Vein with the TGF-a-like ligand, Spitz. There are 3 specific aims: 1) Genetic and biochemical approaches will be used to identify factors that control the biological activity of Vein. 2) The transcriptional control of vein will be investigated by determining if the gene is a direct target of four signaling pathways with which it is known to interact. 3) Differences between Vein and Spitz will be analyzed by comparing the profiles of target-gene induction using DNA microarrays and testing the developmental consequence of substituting the spitz EGF motif for that of vein using homologous recombination. Together, the experiments address a fundamental issue in development concerning how different cell responses are elicited through a single signaling pathway. EGFR (ErbB) tyrosine kinases and their ligands are highly conserved and play important developmental roles in many organisms. Thus, the results found here will have implications beyond Drosophila.
