CRUMBS AND STARDUST, 2 GENES OF DROSOPHILA REQUIRED FOR THE DEVELOPMENT OF EPITHELIAL-CELL POLARITY

Loss-of-function mutations in the Drosophila genes crumbs and stardust are embryonic lethal and cause a breakdown of ectodermally derived ep ithelia during organogenesis, leading to formation of irregular cell c lusters and extensive cell death in some epithelia. The mutant phenoty pe develops gradually and affects the various epithelia to different e xtents. crumbs encodes a large transmembrane protein with 30 EGF-like repeats and four laminin A G-domain-like repeats in its extracellular domain, suggesting its participation in protein-protein interactions. The CRUMBS protein is exclusively expressed on the apical membrane of all ectodermally derived epithelia, the tissues affected in crumbs and stardust mutant embryos. The gene function is completely abolished by a crumbs mutation that causes production of a protein with a truncate d cytoplasmic domain. Instead of being apically localized as in wild-t ype, the mutant CRUMBS protein is diffusely distributed in the cytopla sm; this occurs before any morphologically detectable cellular phenoty pe is visible, suggesting that targeting of proteins is affected in cr umbs mutant embryos. Later, the protein can be detected on the apical and basolateral membranes. Mutations in stardust produce a phenotype n early identical to that associated with crumbs mutations, suggesting t hat both genes are functionally related. Double mutant combinations an d gene dosage studies suggest that both genes are part of a common gen etic pathway, in which stardust acts downstream of crumbs.