title: Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels.
abstract: 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 TGFbeta 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
authors.affiliation: Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Roman
authors.forename: Van N
authors.initials: VN
authors.lastname: Pham
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Lawson
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kulik
authors.forename: Sarah
authors.initials: S
authors.lastname: Childs
authors.forename: Arne C
authors.initials: AC
authors.lastname: Lekven
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Garrity
authors.forename: Randall T
authors.initials: RT
authors.lastname: Moon
authors.forename: Mark C
authors.initials: MC
authors.lastname: Fishman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lechleider
authors.forename: Brant M
authors.initials: BM
authors.lastname: Weinstein
mesh_terms: D029404:Activin Receptors / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001808:Blood Vessels / Q000002:abnormalities / Q000196:embryology*; D002560:Cerebrovascular Circulation; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D006257:Head / Q000098:blood supply* / Q000196:embryology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051785:Smad Proteins; D051902:Smad5 Protein; D051904:Smad8 Protein; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics / Q000503:physiopathology; D015534:Trans-Activators / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C107514:SMAD9 protein, human; D051785:Smad Proteins; D051902:Smad5 Protein; D051904:Smad8 Protein; D015534:Trans-Activators; D029961:Zebrafish Proteins; C497801:smad5 protein, zebrafish; C460101:Acvrl1 protein, zebrafish; D029404:Activin Receptors