PUBLICATION

Alk1 controls arterial endothelial cell migration in lumenized vessels

Authors
Rochon, E.R., Menon, P.G., Roman, B.L.
ID
ZDB-PUB-160612-8
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
  • Apoptosis
  • Animals
  • Cell Proliferation
  • Arteries/cytology*
  • Arteries/metabolism
  • Endothelial Cells/cytology*
  • Endothelial Cells/metabolism*
  • Cell Movement*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/metabolism*
  • Brain/blood supply
  • Coronary Circulation/physiology
  • Zebrafish/metabolism*
  • Endocardium/metabolism
  • Cell Count
  • Heart/physiology
  • Activin Receptors/deficiency
  • Activin Receptors/metabolism*
  • Embryo, Mammalian/metabolism
(all 19)
PubMed
27287800 Full text @ Development
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.
Genes / Markers
Figures
Figure Gallery (6 images)
Show all Figures
Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
pt505Tg; y7TgcontrolPrim-5IFL
pt505Tg; y7TgcontrolPrim-5IFL
pt505Tg; y7Tg + MO3-acvrl1controlPrim-5IFL
pt505Tg; y7Tg + MO3-acvrl1controlPrim-5IFL
y7TgcontrolPrim-15IFL
y7TgcontrolPrim-5IFL
y7TgcontrolPrim-25IFL
y7TgcontrolPrim-5IFL
y7TgcontrolPrim-15IFL
y7TgcontrolPrim-15IFL
1 - 10 of 94
Show
Phenotype
Fish Conditions Stage Phenotype Figure
pt505Tg + MO3-acvrl1controlPrim-5 to Prim-25
pt505Tg + MO3-acvrl1controlPrim-5 to Prim-25
pt505Tg + MO3-acvrl1controlPrim-5 to Prim-25
pt505Tg + MO3-acvrl1controlPrim-5 to Prim-25
pt505Tg + MO3-acvrl1controlPrim-5 to Prim-25
pt505Tg + MO3-acvrl1controlPrim-5 to Prim-25
pt505Tg + MO3-acvrl1controlPrim-5 to Prim-25
pt505Tg; y7Tg + MO3-acvrl1controlPrim-5
pt505Tg; y7Tg + MO3-acvrl1controlPrim-5
rk8Tg; ubs4Tg + MO1-tnnt2acontrolPrim-5 to Long-pec
1 - 10 of 31
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
is4TgTransgenic Insertion
    pt505TgTransgenic Insertion
      pt524TgTransgenic Insertion
        pt525TgTransgenic Insertion
          rk8TgTransgenic Insertion
            ubs4TgTransgenic Insertion
              y6
                		Point Mutation
                y7TgTransgenic Insertion
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  Human Disease Fish Conditions Evidence
                  telangiectasisTAS
                  1 - 1 of 1
                  Show
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  acvrl1MO3-acvrl1MRPHLNO
                  tnnt2aMO1-tnnt2aMRPHLNO
                  1 - 2 of 2
                  Show
                  Fish
                  Fish
                  pt505Tg
                  pt505Tg + MO3-acvrl1
                  pt505Tg; y7Tg
                  pt505Tg; y7Tg + MO3-acvrl1
                  rk8Tg; ubs4Tg
                  rk8Tg; ubs4Tg + MO1-tnnt2a
                  rk8Tg; ubs4Tg + MO3-acvrl1
                  y7Tg
                  y7Tg + MO3-acvrl1
                  1 - 9 of 9
                  Show
                  Antibodies
                  No data available
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  EGFPEFGEGFP
                  GAL4FFEFGGAL4FF
                  KaedeEFGKaede
                  mAGFPEFGmAGFP
                  mCherryEFGmCherry
                  RFPEFGRFP
                  1 - 6 of 6
                  Show
                  Mapping
                  No data available
                  Your Input Welcome
                  We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
                  Citation
                  Rochon, E.R., Menon, P.G., Roman, B.L. (2016) Alk1 controls arterial endothelial cell migration in lumenized vessels. Development (Cambridge, England). 143(14):2593-602.