PUBLICATION
Low Wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice
- Authors
- Benz, F., Wichitnaowarat, V., Lehmann, M., Germano, R.F.V., Mihova, D., Macas, J., Adams, R.H., Taketo, M.M., Guérit, S., Plate, K.H., Vanhollebeke, B., Liebner, S.
- ID
- ZDB-PUB-190402-16
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Vanhollebeke, Benoit
- Keywords
- developmental biology, mouse, zebrafish
- MeSH Terms
-
- Animals
- Capillary Permeability
- Drinking Behavior*
- Endothelial Cells/physiology
- Homeostasis
- Mice, Inbred C57BL
- Subfornical Organ/physiology*
- Water/metabolism*
- Wnt Proteins/metabolism*
- Wnt Signaling Pathway*
- Zebrafish
- Zebrafish Proteins/metabolism
- beta Catenin/metabolism*
- PubMed
- 30932814 Full text @ Elife
Citation
Benz, F., Wichitnaowarat, V., Lehmann, M., Germano, R.F.V., Mihova, D., Macas, J., Adams, R.H., Taketo, M.M., Guérit, S., Plate, K.H., Vanhollebeke, B., Liebner, S. (2019) Low Wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice. eLIFE. 8:.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping