TY  - JOUR
A1  - Liebner, Stefan
A1  - Corada, Monica
A1  - Bangsow, Thorsten
A1  - Babbage, Jane
A1  - Taddei, Andrea
A1  - Czupalla, Cathrin Jacqueline
A1  - Reis, Marco
A1  - Felici, Angelina
A1  - Wolburg, Hartwig
A1  - Fruttiger, Marcus
A1  - Taketo, Makoto Mark
A1  - Melchner, Harald von
A1  - Plate, Karl
A1  - Gerhardt, Holger
A1  - Dejana, Elisabetta
T1  - Wnt/beta-catenin signaling controls development of the blood–brain barrier
T2  - The journal of cell biology
N2  - 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.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6712
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-68153
SN  - 1540-8140
SN  - 0021-9525
N1  - © 2008 Liebner et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
VL  - 183
IS  - 3
SP  - 409
EP  - 417
PB  - Rockefeller Univ. Press
CY  - New York, NY
ER  -