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J Cell Biol. 2008 Nov 3;183(3):409-17. doi: 10.1083/jcb.200806024. Epub 2008 Oct 27.

Wnt/beta-catenin signaling controls development of the blood-brain barrier.

Author information

1
Institute of Neurology (Edinger Institute), Johann Wolfgang Goethe University, 60325 Frankfurt, Germany. elisabetta.dejana@ifom-ieo-campus.it

Abstract

The blood-brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/beta-catenin (beta-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of beta-cat in vivo enhances barrier maturation, whereas inactivation of beta-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of beta-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of beta-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of beta-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown.

PMID:
18955553
PMCID:
PMC2575783
DOI:
10.1083/jcb.200806024
[Indexed for MEDLINE]
Free PMC Article

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