ArticleJournal of molecular and cellular cardiology2024
Epicardial deletion of Sox9 leads to myxomatous valve degeneration and identifies Cd109 as a novel gene associated with valve development.
Article in Journal of molecular and cellular cardiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- SOX6 is expressed in various cell lineages in the developing mouse heart and contributes to proper valvuloseptal development.Anatomical record (Hoboken, N.J. : 2007) · 2026Article
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- CD109 exhibits a dynamic expression pattern in coronary endothelium and endocardial-derived valve mesenchyme during heart development with preserved morphogenesis following endothelial-specific deletion.Frontiers in cell and developmental biology · 2026Article
- Sox9 in the second heart field and the development of the outflow tract; implications for cardiac septation and valve formation.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Role of SOX9 in cardiovascular diseases: Evidence today.World journal of cardiology · 2025Review
- Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development.Cells · 2025Article
- BubR1 Controls Heart Development by Promoting Expression of Cardiogenesis Regulators.Journal of the American Heart Association · 2025Article
- Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025Review
- Sox9 in the epicardium: Implications for cell invasion, differentiation, and coronary vascular development.PloS one · 2025Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Epicardial-derived cells (EPDCs) are involved in the regulation of myocardial growth and coronary vascularization and are critically important for proper development of the atrioventricular (AV) valves. SOX9 is a transcription factor expressed in a variety of epithelial and mesenchymal cells in the developing heart, including EPDCs. To determine the role of SOX9 in epicardial development, an epicardial-specific Sox9 knockout mouse model was generated. Deleting Sox9 from the epicardial cell lineage impairs the ability of EPDCs to invade both the ventricular myocardium and the developing AV valves. After birth, the mitral valves of these mice become myxomatous with associated abnormalities in extracellular matrix organization. This phenotype is reminiscent of that seen in humans with myxomatous mitral valve disease (MVD). An RNA-seq analysis was conducted in an effort to identify genes associated with this myxomatous degeneration. From this experiment, Cd109 was identified as a gene associated with myxomatous valve pathogenesis in this model. Cd109 has never been described in the context of heart development or valve disease. This study highlights the importance of SOX9 in the regulation of epicardial cell invasion-emphasizing the importance of EPDCs in regulating AV valve development and homeostasis-and reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.
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