ArticleDevelopment (Cambridge, England)2016
MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1.
Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 49 citations in OpenAlex.
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- Cardiosphere-Derived Cells from Not Dilated and Dilated Human Myocardium Exhibit Enhanced Metabolic Potential Compared with Conventional Cardiac Mesenchymal Stem/Stromal Cells.International journal of molecular sciences · 2026Article
- Modelling Tetralogy of Fallot: insights and limitations of animal models.Frontiers in cell and developmental biology · 2026Review
- MEF2C controls segment-specific gene regulatory networks that direct heart tube morphogenesis.Genes & development · 2025Article
- Osr1 orchestrates posterior second heart field cell migration for outflow tract formation.Communications biology · 2025Article
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- From Petri Dish to Primitive Heart: How IVF Alters Early Cardiac Gene Networks and Epigenetic Landscapes.Biomedicines · 2025Review
- A retinoic acid:YAP1 signaling axis controls atrial lineage commitment.Cell reports · 2025Article
- Single-cell RNA sequencing profiling of mouse cardiac cells in response to retinoic acid.Heliyon · 2024Article
- In vitro culture alters cell lineage composition and cellular metabolism of bovine blastocyst†.Biology of reproduction · 2024Article
- miR-1 as a Key Epigenetic Regulator in Early Differentiation of Cardiac Sinoatrial Region.International journal of molecular sciences · 2024Article
- Molecular Pathways and Animal Models of d-Transposition of the Great Arteries.Advances in experimental medicine and biology · 2024Review
- Molecular Pathways and Animal Models of Tetralogy of Fallot and Double Outlet Right Ventricle.Advances in experimental medicine and biology · 2024Review
- Drosophila as a Model to Understand Second Heart Field Development.Journal of cardiovascular development and disease · 2023Review
- A Mesp1-dependent developmental breakpoint in transcriptional and epigenomic specification of early cardiac precursors.Development (Cambridge, England) · 2023Article
- The arginine methyltransferase Carm1 is necessary for heart development.G3 (Bethesda, Md.) · 2022Article
- Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.Circulation research · 2022Article
- Unveiling Complexity and Multipotentiality of Early Heart Fields.Circulation research · 2021Article
- Genetics of Transposition of Great Arteries: Between Laterality Abnormality and Outflow Tract Defect.Journal of cardiovascular translational research · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Congenital heart defects are the most common birth defects in humans, and those that affect the proper alignment of the outflow tracts and septation of the ventricles are a highly significant cause of morbidity and mortality in infants. A late differentiating population of cardiac progenitors, referred to as the anterior second heart field (AHF), gives rise to the outflow tract and the majority of the right ventricle and provides an embryological context for understanding cardiac outflow tract alignment and membranous ventricular septal defects. However, the transcriptional pathways controlling AHF development and their roles in congenital heart defects remain incompletely elucidated. Here, we inactivated the gene encoding the transcription factor MEF2C in the AHF in mice. Loss of Mef2c function in the AHF results in a spectrum of outflow tract alignment defects ranging from overriding aorta to double-outlet right ventricle and dextro-transposition of the great arteries. We identify Tdgf1, which encodes a Nodal co-receptor (also known as Cripto), as a direct transcriptional target of MEF2C in the outflow tract via an AHF-restricted Tdgf1 enhancer. Importantly, both the MEF2C and TDGF1 genes are associated with congenital heart defects in humans. Thus, these studies establish a direct transcriptional pathway between the core cardiac transcription factor MEF2C and the human congenital heart disease gene TDGF1. Moreover, we found a range of outflow tract alignment defects resulting from a single genetic lesion, supporting the idea that AHF-derived outflow tract alignment defects may constitute an embryological spectrum rather than distinct anomalies.
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