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ZIRC
ZFIN ID: ZDB-PUB-160612-8
Alk1 controls arterial endothelial cell migration in lumenized vessels
Rochon, E.R., Menon, P.G., Roman, B.L.
Date: 2016
Source: Development (Cambridge, England)   143(14): 2593-602 (Journal)
Registered Authors: Roman, Beth
Keywords: Angiogenesis, Arteriovenous malformation, Alk1/Acvrl1, Endocardium, Hereditary hemorrhagic telangiectasia, Zebrafish
MeSH Terms:
  • Activin Receptors/deficiency
  • Activin Receptors/metabolism*
  • Animals
  • Apoptosis
  • Arteries/cytology*
  • Arteries/metabolism
  • Brain/blood supply
  • Cell Count
  • Cell Movement*
  • Cell Proliferation
  • Coronary Circulation/physiology
  • Embryo, Mammalian/metabolism
  • Endocardium/metabolism
  • Endothelial Cells/cytology*
  • Endothelial Cells/metabolism*
  • Heart/physiology
  • Zebrafish/metabolism*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/metabolism*
PubMed: 27287800 Full text @ Development
FIGURES
ABSTRACT
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.
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