Mosaic eyes gene is required for retinal development

描述（由申请人提供）：我们的长期目标是识别和理解参与视网膜组织，光感受器形态发生和存活的分子和细胞途径。我们正在研究斑马鱼的马赛克眼（moe）基因；moe突变导致视网膜层压失败和视网膜色素上皮（RPE）缺陷。我们发现视网膜上皮细胞组织也不正常；在移动视网膜中，它们在整个上皮中分裂，而不是局限于顶端（RPE）表面。我们通过生成遗传嵌合体表明，移动功能是RPE中相邻视网膜细胞分裂的适当定位所必需的，而不是视网膜细胞本身所必需的（Jensen等人，2001）。

DESCRIPTION (provided by applicant): Our long-term goal is to identify and understand the molecular and cellular pathways involved in retinal organization, and photoreceptor morphogenesis and survival. We are studying the mosaic eyes (moe) gene in zebrafish; mutations in moe cause a failure of retinal lamination and defects in the retinal pigmented epithelial (RPE). We found that retinal epithelial cells are also improperly organized; in moe- retinas they divide throughout the epithelium instead of being localized to apical (RPE) surface. We showed by generating genetic mosaics that moe function is required in the RPE for the proper localization of adjacent retinal cell divisions rather then being required in the retinal cells themselves (Jensen et al., 2001). We cloned the moe locus and it encodes a novel FERM protein (for 4.1 protein, Ezrin, Radixin, Moesin). We provide preliminary evidence that moe acts in the crumbs pathway of apical cell polarity. Mutations in the human Crumbs homologue 1 (Crbl) gene are associated with two severe and early onset retinal degeneration diseases, retinitis pigmentosa 12 (RP12; den Hollander et al., 1999) and Leber's Congenital Amaurosis 1 (LCA1; den Hollander et al., 2001a). Recent work using high-resolution microscopy in vivo, has revealed that the retinas of LCA1 patients are abnormally laminated, a phenotype remarkably similar to the moe mutations. We will test the hypothesis that Moe interacts directly with Crumbs proteins. In Drosophila, crumbs is necessary for photoreceptor morphogenesis (Izaddoost et al., 2002; Pellikka et al., 2002) and the early and severe onset of RP12 may suggest it plays a similar role in vertebrate photoreceptor morphogenesis. Zebrafish moe is expressed in the retina like crbl, suggesting it may cooperate with crbl in photoreceptor morphogenesis. We will test the hypothesis that moe is required for normal photoreceptor morphogenesis. Finally, we will test the hypothesis that moe is required in the RPE for normal retinal lamination.