Low Wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice

  • 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.

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Author:Fabienne Benz, Viraya Wichitnaowarat, Martin Lehmann, Raoul F. V. Germano, Diana Mihova, Jadranka Macas, Ralf Heinrich AdamsORCiD, Makoto Mark Taketo, Sylvaine Guerit, Karl H. Plate, Benoit VanhollebekeORCiD, Stefan Liebner
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30932814
Parent Title (English):eLife
Publisher:eLife Sciences Publications
Place of publication:Cambridge
Contributor(s):Elisabetta Dejana
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/04/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/04/25
Tag:Developmental biology; Mouse; Research article; Zebrafish
Page Number:29
First Page:1
Last Page:29
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.
Institutes:Medizin / Medizin
Exzellenzcluster / Exzellenzcluster Herz-Lungen-System
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0