期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 3, 页码 656-661出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1509834113
关键词
coronary endothelium; septum transversum; proepicardium; Gata4; Wt1
资金
- Ministry of Economy and Competitiveness [BFU2012-35799, ISCIII-RD12/0019-0022, BFU2011-25304]
- European Commission [PITN-GA-2011-289600]
- Junta de Andalucia [CTS-7564]
- Instituto de Salud Carlos III-Fondos FEDER [PI14/00814]
- French Government National Research Agency through the Laboratory of Excellence SIGNALIFE program [ANR-11-LABX-0028-01]
- Association pour la Recherche sur le Cancer [R13026AA-ARC-WAGNER]
- Fondation de France [FDF-U1081-WAGNER]
- Medical Research Council [MC_PC_U127527180] Funding Source: researchfish
- MRC [MC_PC_U127527180] Funding Source: UKRI
Recent reports suggest that mammalian embryonic coronary endothelium (CoE) originates from the sinus venosus and ventricular endocardium. However, the contribution of extracardiac cells to CoE is thought to be minor and nonsignificant for coronary formation. Using classic (Wt1(Cre)) and previously undescribed (G2-Gata4(Cre)) transgenic mouse models for the study of coronary vascular development, we show that extracardiac septum transversum/ proepicardium (ST/PE)-derived endothelial cells are required for the formation of ventricular coronary arterio-venous vascular connections. Our results indicate that at least 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE compartment. Moreover, we show that conditional deletion of the ST/PE lineage-specific Wilms' tumor suppressor gene (Wt1) in the ST/PE ofG2-Gata4(Cre) mice and in the endothelium of Tie2(Cre) mice disrupts embryonic coronary transmural patterning, leading to embryonic death. Taken together, our results demonstrate that ST/PE-derived endothelial cells contribute significantly to and are required for proper coronary vascular morphogenesis.
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