Investigations on the roles of Claudins during zebrafish cardiovascular development

Claudins是闭塞连接内细胞旁通透性的重要调节剂。最近的研究已经开始阐明该蛋白家族的不同成员在未成熟组织中的发育作用。在该项目的第一部分，我们将从功能上表征突出的心内膜或内皮细胞表达的Claudins的作用，以破译Claudins在斑马鱼心脏内膜和内皮发育过程中调节闭塞连接特性的发育相关性。虽然以前的研究主要集中在Claudins在影响胚胎形态发生或生理学的紧密连接特性的调控上，但对Claudins在发育相关信号事件中的潜在参与知之甚少。本项目提案的第二部分旨在详细描述两种斑马鱼Claudin-5蛋白在血管生成信号和心脏发育中的作用。初步的功能研究表明，斑马鱼Claudin-5蛋白在血管生成中的新作用与其已有的屏障形成功能是分开的。

Claudins are essential regulators of paracellular permeability properties within occluding junctions. Recent studies have begun to elucidate the developmental roles of different members of this protein family within immature tissues. In the first part of the project, we will functionally characterize the role of prominent endocardially- or endothelially-expressed Claudins in an approach to decipher the devel-opmental relevance of Claudins in modulating occluding junction properties during zebrafish endocar-dial and endothelial development. Whereas previous studies have mainly focused on the involvement of Claudins in controlling tight junction properties which affect embryonic morphogenesis or physiol-ogy, much less is known about the potential involvement of Claudins in developmentally relevant sig-naling events. The second part of this project proposal aims at a detailed characterization of two ze-brafish Claudin-5 proteins in angiogenesis signaling and cardiac development. Preliminary functional studies suggest novel roles of zebrafish Claudin-5 proteins in angiogenesis that are separate from their well-characterized barrier-forming functions.