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

Authors

  • S. Liebner
  • M. Corada
  • T. Bangsow
  • J. Babbage
  • A. Taddei
  • C.J. Czupalla
  • M. Reis
  • A. Felici
  • H. Wolburg
  • M. Fruttiger
  • M.M. Taketo
  • H. von Melchner
  • K.H. Plate
  • H. Gerhardt
  • E. Dejana

Journal

  • Journal of Cell Biology

Citation

  • J Cell Biol 183 (3): 409-417

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.


DOI

doi:10.1083/jcb.200806024