Crumbs and stardust act in a genetic pathway that controls the organization of epithelia in Drosophila melanogaster

We provide evidence that the genes crumbs (crb) and stardust (sdt) encode critical components of a pathway that acts at the apical pole of epithelial cells to control the cytoarchitecture of ectodermally derived epithelia of the Drosophila embryo. We describe the developmental defects caused by sdt mutations, which are very similar to those associated with mutations in crb. In both mutants the epithelial structure of ectodermal cells breaks down during early organogenesis, leading to the formation of irregular clusters of cells and cell death in some epithelia. Certain cells can, however, compensate for the loss of crb or sdt function in a tissue-specific manner, later reassuming an epithelial cell shape and forming small epithelial vesicles, suggesting that, besides crb and sdt, other tissue-specific components are involved in this process. The crb protein (CRB) is continuously expressed in wild-type embryos in cells of the ectoderm and ectodermally derived epithelia. In sdt mutant embryos CRB is present only during gastrulation, but becomes undetectable during germ band extension; the protein is again visible during early organogenesis, at the time when the sdt mutant phenotype becomes apparent. In sdt mutant embryos, CRB is associated with the apical membrane only in well-differentiated epithelial cells, but it is expressed diffusely in the cytoplasm of cells which have lost epithelial morphology. Our results suggest that time- and tissue-specific control mechanisms exist to establish and maintain epithelial cell structure. Mosaic experiments suggest that sdt is required cell autonomously, in contrast to crb, the requirement of which appears to be non-cell-autonomous. Double mutant combinations of crb and sdt suggest that these genes are part of a common genetic pathway (crb/sdt pathway), in which sdt acts downstream of crb and is activated by the latter.