Disruption ofacvrl1increases endothelial cell number in zebrafish cranial vessels

• DOI: 10.1242/dev.129.12.3009
• Publication Date: 2021-04-26T04:58:15Z
• Authors: Beth L. Roman; Van N. Pham; Nathan D. Lawson; Magdalena Kulik; Sarah Childs; Arne C. Lekven; Deborah M. Garrity; Randall T. Moon; Mark C. Fishman; Robert J. Lechleider; Brant M. Weinstein
• Keywords: Smad5 Protein; 0301 basic medicine; Embryo, Nonmammalian; Sequence Homology, Amino Acid; Activin Receptors; Molecular Sequence Data; Chromosome Mapping; Gene Expression Regulation, Developmental; Smad Proteins; Phosphoproteins; 3. Good health; Animals, Genetically Modified; DNA-Binding Proteins; 03 medical and health sciences; Cerebrovascular Circulation; Smad8 Protein; Mutation; Animals; Blood Vessels; Humans; Amino Acid Sequence; Head; Signal Transduction

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