ArticleHuman molecular genetics2014
Disruption of myocardial Gata4 and Tbx5 results in defects in cardiomyocyte proliferation and atrioventricular septation.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Pooled it
- Review
- Application of Prenatal Whole Exome Sequencing for Congenital Heart Anomalies.International journal of molecular sciences · 2026Review
- TBX5 and CHD4 Coordinately Activate Atrial Cardiomyocyte Genes to Maintain Cardiac Rhythm Homeostasis.Circulation · 2025Article
- Single-nuclei multiomics analysis identifies abnormal cardiomyocytes in a murine model of cardiac development.Nature communications · 2025Article
- Review
- Article
- Cardiomyocyte proliferation and regeneration in congenital heart disease.Pediatric discovery · 2024Article
- Cell-Cycle-Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes.Stem cells (Dayton, Ohio) · 2024Article
- A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network.Circulation · 2024Article
- Promoting cardiomyocyte proliferation for myocardial regeneration in large mammals.Journal of molecular and cellular cardiology · 2024Review
- Analysis of cardiac single-cell RNA-sequencing data can be improved by the use of artificial-intelligence-based tools.Scientific reports · 2023Article
- Single-cell RNA sequencing analysis identifies one subpopulation of endothelial cells that proliferates and another that undergoes the endothelial-mesenchymal transition in regenerating pig hearts.Frontiers in bioengineering and biotechnology · 2023Article
- Translational potential of hiPSCs in predictive modeling of heart development and disease.Birth defects research · 2022Review
- Single-cell transcriptomic profiling unveils dysregulation of cardiac progenitor cells and cardiomyocytes in a mouse model of maternal hyperglycemia.Communications biology · 2022Article
- Towards Understanding the Gene-Specific Roles of GATA Factors in Heart Development: Does GATA4 Lead the Way?International journal of molecular sciences · 2022Review
- Gestational Leucylation Suppresses Embryonic T-Box Transcription Factor 5 Signal and Causes Congenital Heart Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Cardiomyocyte Cell-Cycle Regulation in Neonatal Large Mammals: Single Nucleus RNA-Sequencing Data AnalysisFrontiers in bioengineering and biotechnology · 2022Article
- Transcriptional Regulation of Postnatal Cardiomyocyte Maturation and Regeneration.International journal of molecular sciences · 2021Review
- Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype.Mediators of inflammation · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in GATA4 and TBX5 are associated with congenital heart defects in humans. Interaction between GATA4 and TBX5 is important for normal cardiac septation, but the underlying molecular mechanisms are not well understood. Here, we show that Gata4 and Tbx5 are co-expressed in the embryonic atria and ventricle, but after E15.5, ventricular expression of Tbx5 decreases. Co-localization and co-immunoprecipitation studies demonstrate an interaction of Gata4 and Tbx5 in the developing atria and ventricles, but the ventricular interaction declines after E14.5. Gata4(+/-);Tbx5(+/-) mouse embryos display decreased atrial and ventricular myocardial thickness at E11.5, prior to cardiac septation. To determine the cell lineage in which the interaction was functionally significant in vivo, mice heterozygous for Gata4 in the myocardium or endocardium and heterozygous for Tbx5 (Gata4(MyoDel/wt);Tbx5(+/-) and Gata4(EndoDel/wt);Tbx5(+/-), respectively) were generated. Gata4(MyoDel/wt);Tbx5(+/-) mice displayed embryonic lethality, thin myocardium with reduced cell proliferation, and atrioventricular septation defects similar to Gata4;Tbx5 compound heterozygotes while Gata4(EndoDel/wt);Tbx5(+/-) embryos were normal. Cdk4 and Cdk2, cyclin-dependent kinases required for myocardial development and septation were reduced in Gata4(+/-);Tbx5(+/-) hearts. Cdk4 is a known direct target of Gata4 and the regulation of Cdk2 in the developing heart has not been studied. Chromatin immunoprecipitation and transactivation studies demonstrate that Gata4 and Tbx5 directly regulate Cdk4 while only Tbx5 activates Cdk2 expression. These findings highlight the mechanisms by which disruption of the Gata4 and Tbx5 interaction in the myocardium contributes to cardiac septation defects in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.