Mosaic eyes gene is required for retinal development

视网膜发育需要马赛克眼基因

• 批准号: 7214692
• 负责人: ABIGAIL M JENSEN
• 金额: $ 29.85万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7214692
• 关键词: Mosaic; eyes; gene; required; retinal

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.

描述（由申请人提供）：我们的长期目标是识别和理解视网膜组织、光感受器形态发生和存活所涉及的分子和细胞途径。我们正在研究斑马鱼的马赛克眼（moe）基因； moe 突变会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的组织也不正常；在视网膜中，它们在整个上皮细胞中分裂，而不是局限于顶端（RPE）表面。我们通过生成遗传嵌合体表明，RPE 中需要 Moe 功能才能正确定位相邻视网膜细胞分裂，而不是视网膜细胞本身需要 Moe 功能（Jensen 等人，2001）。 我们克隆了 moe 基因座，它编码一种新的 FERM 蛋白（4.1 蛋白、Ezrin、Radixin、Moesin）。我们提供了初步证据表明 moe 在顶端细胞极性的面包屑途径中发挥作用。人类 Crumbs 同源基因 1 (Crbl) 基因的突变与两种严重的早发性视网膜变性疾病有关：色素性视网膜炎 12（RP12；den Hollander 等，1999）和莱伯先天性黑蒙 1（LCA1；den Hollander 等，1999）。 ，2001a）。最近使用体内高分辨率显微镜的研究表明，LCA1 患者的视网膜异常分层，这种表型与 moe 突变非常相似。 我们将检验 Moe 与 Crumbs 蛋白直接相互作用的假设。在果蝇中，面包屑对于光感受器形态发生是必需的（Izaddoost 等人，2002；Pellikka 等人，2002）并且 RP12 的早期和严重发作可能表明它在脊椎动物光感受器形态发生中发挥类似的作用。斑马鱼 moe 与 crbl 一样在视网膜中表达，表明它可能与 crbl 合作参与光感受器形态发生。我们将检验正常光感受器形态发生需要 moe 的假设。最后，我们将检验 RPE 中需要 moe 来实现正常视网膜分层的假设。