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| 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 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Volume: | 183 |
| Number: | 3 |
| 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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