Reck enables cerebrovascular development by promoting canonical Wnt signaling

  • Florian Ulrich
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University
  • Jorge Carretero-Ortega
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University
  • Javier Menéndez
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University
  • Carlos Narvaez
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University
  • Belinda Sun
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University
  • Eva Lancaster
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University
  • Valerie Pershad
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University
  • Sean Trzaska
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University
  • Evelyn Véliz
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University
  • Makoto Kamei
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development
  • Andrew Prendergast
    Department of Biological Structure, University of Washington
  • Kameha R. Kidd
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development
  • Kenna M. Shaw
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development
  • Daniel A. Castranova
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development
  • Van N. Pham
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development
  • Brigid D. Lo
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development
  • Benjamin L. Martin
    Stony Brook University
  • David W. Raible
    Department of Biological Structure, University of Washington
  • Brant M. Weinstein
    Program in Genomics of Differentiation, National Institute of Child Health and Human Development
  • Jesús Torres-Vázquez
    Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, New York University

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<jats:p>The cerebral vasculature provides the massive blood supply that the brain needs to grow and survive. By acquiring distinctive cellular and molecular characteristics it becomes the Blood Brain Barrier (BBB), a selectively permeable and protective interface between the brain and the peripheral circulation that maintains the extra-cellular milieu permissive for neuronal activity. Accordingly, there is great interest in uncovering the mechanisms that modulate the formation and differentiation of the brain vasculature. By performing a forward genetic screen in zebrafish we isolated no food for thought (nfty72), a recessive late-lethal mutant that lacks most of the intra-cerebral Central Arteries (CtAs), but not other brain blood vessels. We found that the cerebral vascularization deficit of nfty72 is caused by an inactivating lesion in reck (reversion-inducing-cysteine-rich protein with Kazal motifs or ST15; Suppressor of Tumorigenicity 15 protein), which encodes a membrane-anchored tumor suppressor glycoprotein. Our findings highlight Reck as a novel and pivotal modulator of the canonical Wnt signaling pathway that acts in endothelial cells to enable intra-cerebral vascularization and proper expression of molecular markers associated with BBB formation. Additional studies with cultured endothelial cells suggest that, in other contexts, Reck impacts vascular biology via the Vascular Endothelial Growth Factor (VEGF) cascade. Together, our findings have broad implications for both vascular and cancer biology.</jats:p>

収録刊行物

  • Development

    Development 143 147-, 2015-01-01

    The Company of Biologists

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