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Dev Cell. 2015 May 26;33(4):442-54. doi: 10.1016/j.devcel.2015.04.001.

Chemokine-guided angiogenesis directs coronary vasculature formation in zebrafish.

Author information

1
Heart Institute, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA 90027, USA; Program of Developmental Biology and Regenerative Medicine, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
2
Max Planck Institute for Molecular Biomedicine, Muenster 48149, Germany.
3
Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
4
Broad CIRM Center and Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
5
Heart Institute, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA 90027, USA; Program of Developmental Biology and Regenerative Medicine, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA 90027, USA; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Biochemistry & Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: clien@chla.usc.edu.

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.

PMID:
26017769
PMCID:
PMC4448080
DOI:
10.1016/j.devcel.2015.04.001
[Indexed for MEDLINE]
Free PMC Article

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