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
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activin Receptors / genetics*
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Activin Receptors / metabolism*
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Blood Vessels / abnormalities
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Blood Vessels / embryology*
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Cerebrovascular Circulation
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Chromosome Mapping
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DNA-Binding Proteins / metabolism
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Embryo, Nonmammalian
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Gene Expression Regulation, Developmental
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Head / blood supply*
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Head / embryology
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Humans
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Molecular Sequence Data
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Mutation
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Phosphoproteins / metabolism
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Sequence Homology, Amino Acid
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Signal Transduction
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Smad Proteins
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Smad5 Protein
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Smad8 Protein
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Telangiectasia, Hereditary Hemorrhagic / genetics
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Telangiectasia, Hereditary Hemorrhagic / physiopathology
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Trans-Activators / metabolism
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Zebrafish / embryology
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Zebrafish / genetics*
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Zebrafish Proteins / genetics*
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Zebrafish Proteins / metabolism*
Substances
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DNA-Binding Proteins
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Phosphoproteins
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SMAD9 protein, human
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Smad Proteins
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Smad5 Protein
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Smad8 Protein
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Trans-Activators
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Zebrafish Proteins
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smad5 protein, zebrafish
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Acvrl1 protein, zebrafish
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Activin Receptors
Associated data
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GENBANK/AF435024
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GENBANK/AF435025