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Nat Commun. 2018 Nov 19;9(1):4860. doi: 10.1038/s41467-018-07302-x.

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

Author information

1
University of Muenster, Schlossplatz 2, 48149, Muenster, Germany.
2
Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), University of Muenster, Waldeyerstrasse 15, 48149, Muenster, Germany.
3
Université libre de Bruxelles, Rue Prof. Jeener et Brachet 12, 6041, Gosselies, Belgium.
4
Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, 48149, Muenster, Germany.
5
Biozentrum der Universität Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland.
6
Max Planck Institute for Heart and Lung Research, ECCPS Bioinformatics and Deep Sequencing Platform, Ludwigstrasse 43, 61231, Bad Nauheim, Germany.
7
Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Avenue Pasteur 6, 1300, Wavre, Belgium.
8
University of Muenster, Schlossplatz 2, 48149, Muenster, Germany. wiebke.herzog@uni-muenster.de.
9
Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), University of Muenster, Waldeyerstrasse 15, 48149, Muenster, Germany. wiebke.herzog@uni-muenster.de.
10
Max Planck Institute for Molecular Biomedicine, Roentgenstrasse 20, 48149, Muenster, Germany. wiebke.herzog@uni-muenster.de.

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.

PMID:
30451830
PMCID:
PMC6242933
DOI:
10.1038/s41467-018-07302-x
[Indexed for MEDLINE]
Free PMC Article

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