Mosaic Eyes is a novel component of the Crumbs complex and negatively regulates photoreceptor apical size

Abstract

Establishment of apical-basal cell polarity has emerged as an important process during development, and the Crumbs complex is a major component of this process in Drosophila. By comparison, little is known about the role of Crumbs (Crb) proteins in vertebrate development. We show that the FERM protein Mosaic Eyes (Moe) is a novel regulatory component of the Crumbs complex. Moe coimmunoprecipitates with Ome/Crb2a and Nok (Pals1) from adult eye and in vitro interaction experiments suggest these interactions are direct. Morpholino knockdown of ome/crb2a phenocopies the moe mutations. Moe and Crumbs proteins colocalize apically and this apical localization requires reciprocal protein function. By performing genetic mosaic analyses, we show that moe -rod photoreceptors have greatly expanded apical structures, suggesting that Moe is a negative regulator of Crumbs protein function in photoreceptors. We propose that Moe is a crucial regulator of Crumbs protein cell-surface abundance and localization in embryos.

Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa

“…Here, we demonstrated that removal of CRB2 from either Müller glial or photoreceptors has similar effect on the apical complexes. This is partially in consonance with observations in PALS1 mutant mice (31,32), and consistent with the epithelial polarity and adhesion defects seen in both the Drosophila Crb mutant and the zebrafish Crb2a (ome) mutant (12,35,36). Short-term depletion of CRB2 in the adult retinas demonstrated that CRB2 is required for maintenance of the retinal structure.…”

Epithelial cell shape is regulated by Lulu proteins via myosin-II

“…Moe and Yurt (zebrafish and Drosophila Lulu proteins, respectively) were reported to interact with and negatively regulate Crumbs, an apical membrane regulator, thus restricting the apical domain during morphogenesis (Hsu et al, 2006;Laprise et al, 2006). We found here, however, that mammalian Lulu molecules primarily function to upregulate myosin-II activity, which might not be caused by downregulation of Crumbs because, in Lulu2-S expressing cells, the staining signal of apically located Crb3 (a member of vertebrate Crumbs) was not reduced, but significantly enhanced (supplementary material Fig.…”

“…Lulu-mediated negative regulation of Crumbs might therefore take place in specific developmental contexts. The linkage between Lulu and Crumbs is most obvious in photoreceptor cells in both zebrafish and Drosophila (Hsu et al, 2006;Laprise et al, 2006) and it will be interesting to explore the function of Lulu proteins in mammalian photoreceptor morphogenesis, where Lulu might regulate Crumbs.…”

“…In this study, the homologs have been renamed Lulu1 and Lulu2, respectively. In zebrafish, Moe, the sole Lulu molecule in the species, is required for layering of the retina and inflation of the brain ventricles, as well as restricting the photoreceptor apical domain (Hsu et al, 2006;Jensen and Westerfield, 2004). It was shown that Moe interacts with and negatively regulates Crumbs, a regulator of the apical membrane domain, thus regulating the apical membrane size in epithelial structures (Hsu et al, 2006).…”

“…In zebrafish, Moe, the sole Lulu molecule in the species, is required for layering of the retina and inflation of the brain ventricles, as well as restricting the photoreceptor apical domain (Hsu et al, 2006;Jensen and Westerfield, 2004). It was shown that Moe interacts with and negatively regulates Crumbs, a regulator of the apical membrane domain, thus regulating the apical membrane size in epithelial structures (Hsu et al, 2006). Lulu also plays important roles in invertebrates: in Drosophila, mutant animals of Yurt, which is thought from sequence similarity to be an ortholog of Lulu, display failures in early epithelial morphogenesis, including head involution and germ-band elongation (Hoover and Bryant, 2002).…”