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

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/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and...

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Bibliographic Details
Published in:The Journal of cell biology 2008-11, Vol.183 (3), p.409
Main 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
Format: Article
Language:English
Subjects:
Blood vessels
Brain
Cells
Embryology
Genes
Neurons
Online Access:Get full text
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Summary: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/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of β-cat in vivo enhances barrier maturation, whereas inactivation of β-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of β-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 β-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of β-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 ABSTRACT]
ISSN:0021-9525
1540-8140