Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels

• Published in: Development (Cambridge) Vol. 129; no. 12; pp. 3009 - 3019
• Main Authors: Roman, Beth L., Pham, Van N., Lawson, Nathan D., Kulik, Magdalena, Childs, Sarah, Lekven, Arne C., Garrity, Deborah M., Moon, Randall T., Fishman, Mark C., Lechleider, Robert J., Weinstein, Brant M.
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 15.06.2002
• Subjects: Activin Receptors - genetics; Activin Receptors - metabolism; Amino Acid Sequence; Animals; Animals, Genetically Modified; Blood Vessels - abnormalities; Blood Vessels - embryology; Cerebrovascular Circulation; Chromosome Mapping; DNA-Binding Proteins - metabolism; Embryo, Nonmammalian; Freshwater; Gene Expression Regulation, Developmental; Head - blood supply; Head - embryology; Humans; Molecular Sequence Data; Mutation; Phosphoproteins - metabolism; Sequence Homology, Amino Acid; Signal Transduction; Smad Proteins; Smad5 Protein; Smad8 Protein; Telangiectasia, Hereditary Hemorrhagic - genetics; Telangiectasia, Hereditary Hemorrhagic - physiopathology; Trans-Activators - metabolism; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.129.12.3009

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. Movies available on-line