SOX6 is expressed in various cell lineages in the developing mouse heart and contributes to proper valvuloseptal development

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Cells derived from the endocardium, epicardium, cardiac neural crest, and second heart field play a critical role in the formation of the valvuloseptal structures of the heart. Previous studies have shown that the expression of the transcription factor SOX9 in these cell populations is essential in the regulation of this process. SOX9 interacts with other SOX family members including SOX5 and SOX6 to cooperatively regulate other developmental events. Although SOX6 has documented roles in the postnatal heart, its role in cardiac development has not yet been examined. For the current study we decided to investigate the importance of SOX6 in valvuloseptal morphogenesis. Expression studies revealed that SOX6 is expressed in many of the cell lineages that contribute to the formation of the heart. Given the pattern of SOX6 expression in the endocardium and endocardial-derived cells as well as in the coronary endothelium, we focused on the role of SOX6 in these cell populations by generating endothelial/endocardial-specific Sox6 knockout mice. These conditional knockout mice presented with ventricular septal defects, enlarged atrioventricular valves, and coronary abnormalities. Cardiovascular defects observed in the endothelial/endocardial-specific Sox6 knockout mouse demonstrate that SOX6 plays an important role in valvuloseptal development.

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