Work

Sox9 in the second heart field and the development of the outflow tract; implications for cardiac septation and valve formation

Year: 2025

Type: article

Abstract: BACKGROUND: Previously, we explored the role of Sox9 in the second heart field (SHF) in atrioventricular septation. For that study, we created a SHF-specific Sox9 knockout mouse. In addition to the presence of primary atrial septal defects in half of the offspring, we found that virtually all specimens also developed a ventricular septal defect. Histological analysis suggested that the ventricular septal defects resulted from developmental perturbation of the mesenchymal structures within the outflow tract. In the current study, we investigated the role of Sox9 in the SHF in the development of these tissues. RESULTS: Sox9 is expressed in all mesenchymal cell populations in the developing outflow tract, including a cohort of endocardial-derived cells that originate from the SHF-derived endocardium. SHF-specific deletion of Sox9 inhibits the formation of this cell population and ultimately leads to truncation of the mesenchymal outlet septum. This prevents complete fusion of this outlet septum with the atrioventricular mesenchymal complex, resulting in ventricular septal defects. CONCLUSIONS: In combination with our first paper on the role of Sox9 in atrioventricular septation, data presented in this study demonstrate that Sox9 expression in the SHF is of critical importance for the proper formation of the septal structures in the developing heart.

Source: Developmental Dynamics

DOI: 10.1002/dvdy.70014