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

Item Type:Article
Title:Wnt/β-catenin signaling controls development of the blood-brain barrier
Creators Name:Liebner, S. and Corada, M. and Bangsow, T. and Babbage, J. and Taddei, A. and Czupalla, C.J. and Reis, M. and Felici, A. and Wolburg, H. and Fruttiger, M. and Taketo, M.M. and von Melchner, H. and Plate, K.H. and Gerhardt, H. and Dejana, E.
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 (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 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 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.
Keywords:Animal Models, Blood-Brain Barrier, Central Nervous System, Cerebrovascular Circulation, Physiologic Neovascularization, Reporter Genes, Signal Transduction, Wnt Proteins, beta Catenin, beta-Galactosidase, Animals, Mice
Source:Journal of Cell Biology
Publisher:Rockefeller University Press
Page Range:409-417
Date:3 November 2008
Official Publication:https://doi.org/10.1083/jcb.200806024
PubMed:View item in PubMed

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