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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., Corada, M., Bangsow, T., Babbage, J., Taddei, A., Czupalla, C.J., Reis, M., Felici, A., Wolburg, H., Fruttiger, M., Taketo, M.M., von Melchner, H., Plate, K.H., 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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