Ivins, S;
Chappell, J;
Vernay, B;
Suntharalingham, J;
Martineau, A;
Mohun, TJ;
Scambler, PJ;
(2015)
The CXCL12/CXCR4 Axis Plays a Critical Role in Coronary Artery Development.
Developmental Cell
, 33
(4)
pp. 455-468.
10.1016/j.devcel.2015.03.026.
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Abstract
The chemokine CXCL12 and its receptor CXCR4 have many functions during embryonic and post-natal life. We used murine models to investigate the role of CXCL12/CXCR4 signaling in cardiac development and found that embryonic Cxcl12-null hearts lacked intra-ventricular coronary arteries (CAs) and exhibited absent or misplaced CA stems. We traced the origin of this phenotype to defects in the early stages of CA stem formation. CA stems derive from the peritruncal plexus, an encircling capillary network that invades the wall of the developing aorta. We showed that CXCL12 is present at high levels in the outflow tract, while peritruncal endothelial cells (ECs) express CXCR4. In the absence of CXCL12, ECs were abnormally localized and impaired in their ability to anastomose with the aortic lumen. We propose that CXCL12 is required for connection of peritruncal plexus ECs to the aortic endothelium and thus plays a vital role in CA formation.
| Type: | Article |
|---|---|
| Title: | The CXCL12/CXCR4 Axis Plays a Critical Role in Coronary Artery Development |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.devcel.2015.03.026 |
| Publisher version: | http://dx.doi.org/10.1016/j.devcel.2015.03.026 |
| Language: | English |
| Additional information: | © 2015 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
| Keywords: | Animals, Aorta, Cells, Cultured, Chemokine CXCL12, Coronary Vessels, Embryo, Mammalian, Endothelium, Vascular, Female, Heart, In Situ Hybridization, Male, Mice, Mice, Knockout, Organogenesis, Receptors, CXCR4, Signal Transduction |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1472418 |
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