Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels.
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
Roman
Beth L
BL
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Pham
Van N
VN
Lawson
Nathan D
ND
Kulik
Magdalena
M
Childs
Sarah
S
Lekven
Arne C
AC
Garrity
Deborah M
DM
Moon
Randall T
RT
Fishman
Mark C
MC
Lechleider
Robert J
RJ
Weinstein
Brant M
BM
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*
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