9318242 Bier The goal of this proposal is to understand the function of the rhomboid (rho) gene that is required for several distinct developmental events including : early dorsal- ventral pattern formation in the Drosophila embryo, the formation of embryonic sensory organs, and the formation of adult wing veins. rho is one of several genes (referred to as ventro-lateral group genes) required for the formation of these diverse structures. Other ventro-lateral group genes encode an EGF/TGF alpha type of growth factor (spitz) and the Drosophila EGF-receptor (egf-r). rho is the only known member of the ventro-lateral group of genes expressed in a spatially localized pattern corresponding to the cells requiring the activity of ventro-lateral group genes. rho encodes a membrane protein (Rho) and may act by amplifying EGF-R signaling in response to binding the Spitz growth factor. Because the EGF-R signaling pathway has been highly conserved during evolution it is likely that these studies in Drosophila will be directly relevant to other species, including humans. The following are specific research goals for this proposal: 1) Determine the subcellular localization of the Rho protein. Is the Rho protein located on the cell surface as predicted for a protein functioning as part of a receptor complex? Is Rho located at sites of intimate cell- cell contact? 2) Investigate how the Rho protein functions biochemically and determine whether Rho physically interacts with other proteins. Does the Rho protein physically interact with other proteins (e.g. components of the EGF-R signaling pathway)? Is Spi a ligand for EGF-R? Does Rho mediate differential cell adhesion? 3) Determine whether rho is dedicated to amplifying Spi-EGF-R signaling or are other signaling pathways also activated by Rho? Does transcriptional down regulation of components of the EGF-R pathway depend on rho? ***
