TY - JOUR A1 - Benz, Fabienne A1 - Wichitnaowarat, Viraya A1 - Lehmann, Martin A1 - Germano, Raoul F. V. A1 - Mihova, Diana A1 - Macas, Jadranka A1 - Adams, Ralf Heinrich A1 - Taketo, Makoto Mark A1 - Guerit, Sylvaine A1 - Plate, Karl A1 - Vanhollebeke, Benoit A1 - Liebner, Stefan T1 - Low Wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice T2 - eLife N2 - The circumventricular organs (CVOs) in the central nervous system (CNS) lack a vascular blood-brain barrier (BBB), creating communication sites for sensory or secretory neurons, involved in body homeostasis. Wnt/β-catenin signaling is essential for BBB development and maintenance in endothelial cells (ECs) in most CNS vessels. Here we show that in mouse development, as well as in adult mouse and zebrafish, CVO ECs rendered Wnt-reporter negative, suggesting low level pathway activity. Characterization of the subfornical organ (SFO) vasculature revealed heterogenous claudin-5 (Cldn5) and Plvap/Meca32 expression indicative for tight and leaky vessels, respectively. Dominant, EC-specific β-catenin transcription in mice, converted phenotypically leaky into BBB-like vessels, by augmenting Cldn5+ vessels, stabilizing junctions and by reducing Plvap/Meca32+ and fenestrated vessels, resulting in decreased tracer permeability. Endothelial tightening augmented neuronal activity in the SFO of water restricted mice. Hence, regulating the SFO vessel barrier may influence neuronal function in the context of water homeostasis. KW - Research article KW - Developmental biology KW - Mouse KW - Zebrafish Y1 - 2019 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50162 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-501628 SN - 2050-084X N1 - Copyright Benz et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. VL - 8 IS - e43818 SP - 1 EP - 29 PB - eLife Sciences Publications CY - Cambridge ER -