Alk1 controls arterial endothelial cell migration in lumenized vessels

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  • Elizabeth R. Rochon
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
  • Prahlad G. Menon
    Department of Biomedical Engineering, Duquesne University, Pittsburgh, PA 15110, USA
  • Beth L. Roman
    Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA

Description

<jats:p>Heterozygous loss of the arterial-specific TGF-β type I receptor, activin receptor-like kinase 1 (ALK1), causes hereditary hemorrhagic telangiectasia (HHT). HHT is characterized by development of fragile, direct connections between arteries and veins, or arteriovenous malformations (AVMs). However, how decreased ALK1 signaling leads to AVMs is unknown. To understand the cellular missteps that cause AVMs, we assessed endothelial cell behavior in alk1-deficient zebrafish embryos, which develop cranial AVMs. Our data demonstrate that alk1 loss has no effect on arterial endothelial cell proliferation but alters arterial endothelial cell migration within lumenized vessels. In wild type embryos, alk1-positive cranial arterial endothelial cells generally migrate toward the heart, against the direction of blood flow, with some cells incorporating into endocardium. In alk1-deficient embryos, migration against flow is dampened and migration in the direction of flow is enhanced. Altered migration results in decreased endothelial cell number in arterial segments proximal to the heart and increased endothelial cell number in arterial segments distal to the heart. We speculate that the consequent increase in distal arterial caliber and hemodynamic load precipitates the flow-dependent development of downstream AVMs.</jats:p>

Journal

  • Development

    Development 143 2593-, 2016-01-01

    The Company of Biologists

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