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Updated: Mar 27, 2026
Analysis of Coronary Vessels in Cleared Embryonic Hearts
Published on: December 7, 2016
Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio-venous connections
Elena Cano1, Rita Carmona2, Adrián Ruiz-Villalba3
1Department of Animal Biology, Faculty of Sciences, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Málaga, 29071 Málaga, Spain; Group of Cardiovascular Genetics, Department of Vertebrate Genomics and Cardiovascular Genetics, Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin 13125, Germany; Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany;
Insights
Extracardiac endothelial cells from the septum transversum/proepicardium are crucial for forming coronary vascular connections in developing mouse hearts. Their significant contribution is essential for proper coronary development and embryonic survival.
Area of Science:
- Developmental biology
- Cardiovascular research
- Genetics
Background:
- Mammalian embryonic coronary endothelium (CoE) was previously thought to originate mainly from the sinus venosus and ventricular endocardium.
- The contribution of extracardiac cells to CoE was considered minor and insignificant for coronary formation.
Purpose of the Study:
- To investigate the contribution of extracardiac cells to embryonic coronary vascular development.
- To determine the role of septum transversum/proepicardium (ST/PE)-derived endothelial cells in coronary formation.
Main Methods:
- Utilized Wt1(Cre) and G2-Gata4(Cre) transgenic mouse models for studying coronary vascular development.
- Investigated the role of Wilms' tumor suppressor gene (Wt1) in ST/PE and endothelial cells using conditional deletion strategies.
Main Results:
- Demonstrated that extracardiac ST/PE-derived endothelial cells are required for forming ventricular coronary arterio-venous vascular connections.
- Showed that at least 20% of embryonic coronary arterial and capillary endothelial cells originate from the ST/PE.
- Found that conditional deletion of Wt1 in ST/PE or endothelium disrupts coronary patterning, leading to embryonic lethality.
Conclusions:
- ST/PE-derived endothelial cells significantly contribute to and are essential for proper coronary vascular morphogenesis.
- This study redefines the understanding of coronary endothelium origin and highlights the critical role of extracardiac progenitors.
Abstract:
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 of G2-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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