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Science 322 (5905): 1247-1250

Copyright © 2008 by the American Association for the Advancement of Science

Canonical Wnt Signaling Regulates Organ-Specific Assembly and Differentiation of CNS Vasculature

Jan M. Stenman,1* Jay Rajagopal,1,2 Thomas J. Carroll,1{dagger} Makoto Ishibashi,1{ddagger} Jill McMahon,1 Andrew P. McMahon1,3§

Abstract: Every organ depends on blood vessels for oxygen and nutrients, but the vasculature associated with individual organs can be structurally and molecularly diverse. The central nervous system (CNS) vasculature consists of a tightly sealed endothelium that forms the blood-brain barrier, whereas blood vessels of other organs are more porous. Wnt7a and Wnt7b encode two Wnt ligands produced by the neuroepithelium of the developing CNS coincident with vascular invasion. Using genetic mouse models, we found that these ligands directly target the vascular endothelium and that the CNS uses the canonical Wnt signaling pathway to promote formation and CNS-specific differentiation of the organ's vasculature.

1 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
2 Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
3 Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.

* Present address: Ludwig Institute for Cancer Research, Karolinska Institute, Box 240, SE-171 77 Stockholm, Sweden.

{dagger} Present address: Department of Internal Medicine (Nephrology) and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

{ddagger} Present address: Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.

§ To whom correspondence should be addressed. E-mail: mcmahon{at}mcb.harvard.edu


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