PUBLICATION

Chemokine-guided angiogenesis directs coronary vasculature formation in zebrafish

Authors
Harrison, M.R., Bussmann, J., Huang, Y., Zhao, L., Osorio, A., Burns, C.G., Burns, C.E., Sucov, H.M., Siekmann, A.F., Lien, C.L.
ID
ZDB-PUB-150529-6
Date
2015
Source
Developmental Cell   33: 442-54 (Journal)
Registered Authors
Burns (Erter), Caroline, Burns, Geoff, Bussmann, Jeroen, Harrison, Michael, Lien, Ching-Ling (Ellen), Siekmann, Arndt Friedrich, Sucov, Henry M., Zhao, Long
Keywords
none
MeSH Terms
  • Angiography
  • Animals
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/growth & development*
  • Animals, Genetically Modified/metabolism
  • Chemokines, CXC/metabolism*
  • Coronary Vessels/embryology
  • Coronary Vessels/growth & development*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism*
  • Endothelium, Vascular/cytology
  • Endothelium, Vascular/metabolism
  • Gene Expression Regulation, Developmental
  • Heart/physiology
  • Microscopy, Confocal
  • Neovascularization, Physiologic*
  • Organogenesis/physiology
  • Receptors, CXCR4/metabolism*
  • Regeneration/physiology
  • Signal Transduction
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism*
PubMed
26017769 Full text @ Dev. Cell
Abstract
Interruption of the coronary blood supply severely impairs heart function with often fatal consequences for patients. However, the formation and maturation of these coronary vessels is not fully understood. Here we provide a detailed analysis of coronary vessel development in zebrafish. We observe that coronary vessels form in zebrafish by angiogenic sprouting of arterial cells derived from the endocardium at the atrioventricular canal. Endothelial cells express the CXC-motif chemokine receptor Cxcr4a and migrate to vascularize the ventricle under the guidance of the myocardium-expressed ligand Cxcl12b. cxcr4a mutant zebrafish fail to form a vascular network, whereas ectopic expression of Cxcl12b ligand induces coronary vessel formation. Importantly, cxcr4a mutant zebrafish fail to undergo heart regeneration following injury. Our results suggest that chemokine signaling has an essential role in coronary vessel formation by directing migration of endocardium-derived endothelial cells. Poorly developed vasculature in cxcr4a mutants likely underlies decreased regenerative potential in adults.
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