The rho gene (Bier et al., 1990) encodes a novel integral membrane protein (Rho) (Sturtevant et al., 1996) that potentiates EGF-Receptor (EGF-R) signaling (Fig. 4) in localized patterns during embryogenesis and adult development (Sturtevant et al., 1993; Noll et al., 1994). For example, rho is expressed in broad lateral stripes in the neuroectoderm of blastoderm embryos and, in rho- mutants, epithelial cells derived from the neuroectoderm fail to differentiate(Bier et al., 1990). Similarly, rho is expressed in wing vein primordia during wing development and is required for vein formation (Sturtevant et al., 1993). In contrast, genes encoding other components of the EGF-R pathway are ubiquitously expressed, consistent with a low basal requirement for EGF-R signaling in all epithelial cells. When rho is mis-expressed, EGF-R signaling is hyperactivated correspondingly and cell fates are transformed accordingly (Sturtevant et al., 1993; Noll et al., 1994).
The Rho protein is highly concentrated in plaque-like structures at the apical cell surface (Sturtevant et al., 1996). Electron microscopy reveals that Rho protein is found in all compartments of the secretory pathway as well as in large structures at the cell surface. These cell surface structures, which most likely correspond to the large plaque-like structures visible by light microscopy, are comprised of patches of plasma membrane and masses of material with a vesicular appearance directly underlying the membrane patches. Rho plaques may define specialized sites at which EGF-R signaling is potentiated (Fig. 4). One mechanism for potentiation of EGF-R signaling could be cleavage of the membrane bound precursor form of the EGF-R ligand to generate a more active secreted form of ligand.
Major experimental goals for rho are to identify proteins interacting physically with Rho, to investigate the significance of the unusual subcellular distribution of the Rho protein in superficial plaque-like structures, and to define functional domains of the Rho protein through a combination of site-directed and in vivo mutagenesis.
