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- Title
Wnt/beta-catenin signaling controls development of the blood-brain barrier.
- Authors
Liebner, Stefan; Corada, Monica; Bangsow, Thorsten; Babbage, Jane; Taddei, Andrea; Czupalla, Cathrin J; Reis, Marco; Felici, Angelina; Wolburg, Hartwig; Fruttiger, Marcus; Taketo, Makoto M; von Melchner, Harald; Plate, Karl Heinz; Gerhardt, Holger; Dejana, Elisabetta
- 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.
- Publication
The Journal of cell biology, 2008, Vol 183, Issue 3, p409
- ISSN
1540-8140
- Publication type
Journal Article
- DOI
10.1083/jcb.200806024