Disruption of<i>acvrl1</i>increases endothelial cell number in zebrafish cranial vessels

  • Beth L. Roman
    Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
  • Van N. Pham
    Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
  • Nathan D. Lawson
    Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
  • Magdalena Kulik
    Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
  • Sarah Childs
    Cardiovascular Research Center, Massachusetts General Hospital East, Charlestown, MA 02129, USA
  • Arne C. Lekven
    Howard Hughes Medical Institute and Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98185 USA
  • Deborah M. Garrity
    Cardiovascular Research Center, Massachusetts General Hospital East, Charlestown, MA 02129, USA
  • Randall T. Moon
    Howard Hughes Medical Institute and Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98185 USA
  • Mark C. Fishman
    Cardiovascular Research Center, Massachusetts General Hospital East, Charlestown, MA 02129, USA
  • Robert J. Lechleider
    Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
  • Brant M. Weinstein
    Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA

説明

<jats:p>The zebrafish mutant violet beauregarde (vbg) can be identified at two days post-fertilization by an abnormal circulation pattern in which most blood cells flow through a limited number of dilated cranial vessels and fail to perfuse the trunk and tail. This phenotype cannot be explained by caudal vessel abnormalities or by a defect in cranial vessel patterning, but instead stems from an increase in endothelial cell number in specific cranial vessels. We show that vbg encodes activin receptor-like kinase 1 (Acvrl1; also known as Alk1), a TGFβ type I receptor that is expressed predominantly in the endothelium of the vessels that become dilated in vbg mutants. Thus, vbg provides a model for the human autosomal dominant disorder, hereditary hemorrhagic telangiectasia type 2, in which disruption of ACVRL1 causes vessel malformations that may result in hemorrhage or stroke.</jats:p><jats:p>Movies available on-line</jats:p>

収録刊行物

  • Development

    Development 129 (12), 3009-3019, 2002-06-15

    The Company of Biologists

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