Investigations on the roles of Claudins during zebrafish cardiovascular development

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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.