Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio–venous connections

Elena Cano, Rita Carmona, Adrián Ruiz-Villalba, Anabel Rojas, You-Ying Chau, Kay D Wagner, Nicole Wagner, Nicholas D Hastie, Ramón Muñoz-Chápuli, José M Pérez-Pomares

Research output: Contribution to journalArticlepeer-review


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 (Wt1Cre) and previously undescribed (G2-Gata4Cre) 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-Gata4Cre mice and in the endothelium of Tie2Cre 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.

Original languageEnglish
Pages (from-to)656-661
JournalProceedings of the National Academy of Sciences (PNAS)
Issue number3
Early online date6 Jan 2016
Publication statusPublished - 19 Jan 2016


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