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Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):641-6. doi: 10.1073/pnas.0805165106. Epub 2009 Jan 7.

Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis.

Author information

1
Stanford University School of Medicine, Department of Developmental Biology, Stanford, CA 94305, USA. Rdaneman@stanford.edu

Erratum in

  • Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6422.

Abstract

Despite the importance of CNS blood vessels, the molecular mechanisms that regulate CNS angiogenesis and blood-brain barrier (BBB) formation are largely unknown. Here we analyze the role of Wnt/beta-catenin signaling in regulating the formation of CNS blood vessels. First, through the analysis of TOP-Gal Wnt reporter mice, we identify that canonical Wnt/beta-catenin signaling is specifically activated in CNS, but not non-CNS, blood vessels during development. This activation correlates with the expression of different Wnt ligands by neural progenitor cells in distinct locations throughout the CNS, including Wnt7a and Wnt7b in ventral regions and Wnt1, Wnt3, Wnt3a, and Wnt4 in dorsal regions. Blockade of Wnt/beta-catenin signaling in vivo specifically disrupts CNS, but not non-CNS, angiogenesis. These defects include reduction in vessel number, loss of capillary beds, and the formation of hemorrhagic vascular malformations that remain adherent to the meninges. Furthermore, we demonstrate that Wnt/beta-catenin signaling regulates the expression of the BBB-specific glucose transporter glut-1. Taken together these experiments reveal an essential role for Wnt/beta-catenin signaling in driving CNS-specific angiogenesis and provide molecular evidence that angiogenesis and BBB formation are in part linked.

PMID:
19129494
PMCID:
PMC2626756
DOI:
10.1073/pnas.0805165106
[Indexed for MEDLINE]
Free PMC Article

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