晶状体中Crb复合物调控细胞运动与粘连的机制研究

Vertebrate lens is derived from epithelia. Cataract is one of the major causes that lead to visual impairment and blindness. The abnormality of epithelial migration, organization and cell state transition causes cataract. However the mechanisms which regulate lens epithelia cell state transition is not fully understood. Crb complex is a key element that determines epithelial polarity. It is known that Crb complex play essential roles during epithelia cell state transition. The molecular mechanism remains to be discovered. Our preliminary data has suggested that Crb complex may directly recruit cellular adhesion molecules related vesicle trafficking protein Rab11, thus play important roles on the reorganization of intercellular adhesion of lens cells. The failure of intracellular adhesion reorganization leads the irregular cell migration and organization, resulting in cataract. In this proposal we will integrate multiple technologies in genetics, molecular and cell biology, TEM and statistics to verify our hypothesis in zebrafish. The results shall benefit our understanding of the pathology and therapy of cataract.

晶状体上皮细胞的转化、迁移或增殖等方面异常是导致白内障的重要原因之一。近年来干细胞技术的发展为理解白内障的发病机制与防治提供了新的思路。深入分析具有干性的晶状体上皮细胞的组织、迁移与细胞状态的转化等规律及调节因素，对理解相关白内障的发病机制，和进一步探索采用干细胞等技术预防与治疗白内障的新方案具有重要的启示和指导意义。目前对晶状体上皮细胞的状态转化的调控机制还有待更深入的研究。Crb复合物是决定上皮细胞极性的关键因子，在上皮细胞状态转化与细胞运动中起重要作用，但具体机制仍不明确。课题组前期研究发现，Crb复合物可能通过定向招募细胞粘连蛋白相关的囊泡运输蛋白Rab11，从而决定细胞粘连的重组，进而影响晶状体细胞的运动和组织。Crb复合物功能异常将造成白内障样表型。本项目将对这一假说予以证明。本项目的顺利开展将为白内障的预防与治疗提供新思路。