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Establishment of a neuroepithelial barrier by Claudin5a is essential for zebrafish brain ventricular lumen expansion

Item Type:Article
Title:Establishment of a neuroepithelial barrier by Claudin5a is essential for zebrafish brain ventricular lumen expansion
Creators Name:Zhang, J., Piontek, J., Wolburg, H., Piehl, C., Liss, M., Otten, C., Christ, A., Willnow, T.E., Blasig, I.E. and Abdelilah-Seyfried, S.
Abstract:Lumen expansion driven by hydrostatic pressure occurs during many morphogenetic processes. Although it is well established that members of the Claudin family of transmembrane tight junction proteins determine paracellular tightness within epithelial/endothelial barrier systems, functional evidence for their role in the morphogenesis of lumenized organs has been scarce. Here, we identify Claudin5a as a core component of an early cerebral-ventricular barrier system that is required for ventricular lumen expansion in the zebrafish embryonic brain before the establishment of the embryonic blood-brain barrier. Loss of Claudin5a or expression of a tight junction-opening Claudin5a mutant reduces brain ventricular volume expansion without disrupting the polarized organization of the neuroepithelium. Perfusion experiments with the electron-dense small molecule lanthanum nitrate reveal that paracellular tightness of the cerebral-ventricular barrier decreases upon loss of Claudin5a. Genetic analyses show that the apical neuroepithelial localization of Claudin5a depends on epithelial cell polarity and provide evidence for concerted activities between Claudin5a and Na(+),K(+)-ATPase during luminal expansion of brain ventricles. These data establish an essential role of a barrier-forming Claudin in ventricular lumen expansion, thereby contributing to brain morphogenesis.
Keywords:Brain Morphogenesis, Lumen Formation, Na(+),K(+)-ATPase, Tight Junctions, Cell Polarity, Animals, Mice, Zebrafish
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:1425-1430
Date:26 January 2010
Official Publication:https://doi.org/10.1073/pnas.0911996107
PubMed:View item in PubMed

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