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Wnt/β-catenin signaling regulates VE-cadherin-mediated anastomosis of brain capillaries by counteracting S1pr1 signaling

Hübner, Kathleen and Cabochette, Pauline and Diéguez-Hurtado, Rodrigo and Wiesner, Cora and Wakayama, Yuki and Grassme, Kathrin S. and Hubert, Marvin and Guenther, Stefan and Belting, Heinz-Georg and Affolter, Markus and Adams, Ralf H. and Vanhollebeke, Benoit and Herzog, Wiebke. (2018) Wnt/β-catenin signaling regulates VE-cadherin-mediated anastomosis of brain capillaries by counteracting S1pr1 signaling. Nature communications, 9 (1). p. 4860.

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Official URL: https://edoc.unibas.ch/66886/

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Abstract

Canonical Wnt signaling is crucial for vascularization of the central nervous system and blood-brain barrier (BBB) formation. BBB formation and modulation are not only important for development, but also relevant for vascular and neurodegenerative diseases. However, there is little understanding of how Wnt signaling contributes to brain angiogenesis and BBB formation. Here we show, using high resolution in vivo imaging and temporal and spatial manipulation of Wnt signaling, different requirements for Wnt signaling during brain angiogenesis and BBB formation. In the absence of Wnt signaling, premature Sphingosine-1-phosphate receptor (S1pr) signaling reduces VE-cadherin and Esama at cell-cell junctions. We suggest that Wnt signaling suppresses S1pr signaling during angiogenesis to enable the dynamic junction formation during anastomosis, whereas later S1pr signaling regulates BBB maturation and VE-cadherin stabilization. Our data provides a link between brain angiogenesis and BBB formation and identifies Wnt signaling as coordinator of the timing and as regulator of anastomosis.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)
UniBasel Contributors:Affolter, Markus
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Apr 2020 19:12
Deposited On:26 Apr 2020 19:12

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