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

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 un...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2016-01, Vol.113 (3), p.656-661
Hauptverfasser: Cano, Elena, Carmona, Rita, Ruiz-Villalba, Adrián, Rojas, Anabel, Chau, You-Ying, Wagner, Kay D., Wagner, Nicole, Hastie, Nicholas D., Muñoz-Chápuli, Ramón, Pérez-Pomares, José M.
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container_title Proceedings of the National Academy of Sciences - PNAS
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creator Cano, Elena
Carmona, Rita
Ruiz-Villalba, Adrián
Rojas, Anabel
Chau, You-Ying
Wagner, Kay D.
Wagner, Nicole
Hastie, Nicholas D.
Muñoz-Chápuli, Ramón
Pérez-Pomares, José M.
description 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.
doi_str_mv 10.1073/pnas.1509834113
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subjects Animals
Biological Sciences
Biomarkers - metabolism
Cell Lineage
Cells
Coronary Vessels - cytology
Coronary Vessels - embryology
Embryo, Mammalian - cytology
Embryonic Development
Endothelial Cells - cytology
Enhancer Elements, Genetic - genetics
Epithelial-Mesenchymal Transition
GATA4 Transcription Factor - metabolism
Gene Deletion
Genes
Genes, Reporter
Green Fluorescent Proteins - metabolism
Heart
Heart Septum - cytology
Integrases - metabolism
Mice
Models, Biological
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
Pericardium - cytology
Phenotype
Rodents
Tumors
WT1 Proteins - metabolism
title Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio–venous connections
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