Journal
ELIFE
Volume 8, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.43818
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Funding
- Deutsche Forschungsgemeinschaft [LI 911/5-1]
- Horizon 2020 Framework Programme [BtRAIN]
- Goethe University Frankfurt - Line A
- Landes-Offensive zur Entwicklung Wissenschaftlich-okonomischer Exzellenz (LOEWE), Program of the Center for Personalized Translational Epilepsy Research, CePTER [TP8]
- German Centre for Heart and Circulation Research (DZHK)
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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/beta-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 beta-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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