ArticleDevelopment (Cambridge, England)2005
T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis.
Article in Development (Cambridge, England), 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 227 citations in OpenAlex.
- Rejuvenating the damaged and aged heart: lessons from development.npj biomedical innovations · 2026Review
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Transcriptomic profiling of cardiac development in Bama Xiang pigs across key developmental stages.Zoological research · 2025Article
- Genetic and functional variants of the TBX20 gene promoter in dilated cardiomyopathy.Molecular genetics & genomic medicine · 2024Article
- Drosophila as a Model to Understand Second Heart Field Development.Journal of cardiovascular development and disease · 2023Review
- The Tbx20-TLE interaction is essential for the maintenance of the second heart field.Development (Cambridge, England) · 2023Article
- Activation of XBP1 but not ATF6α rescues heart failure induced by persistent ER stress in medaka fish.Life science alliance · 2023Article
- Epigenetic Evaluation of theCells · 2023Article
- TBX20 Improves Contractility and Mitochondrial Function During Direct Human Cardiac Reprogramming.Circulation · 2022Article
- Endocardial Regulation of Cardiac Development.Journal of cardiovascular development and disease · 2022Review
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Single-Nucleotide Polymorphisms in Exonic and Promoter Regions of Transcription Factors of Second Heart Field Associated with Sporadic Congenital Cardiac Anomalies.Balkan journal of medical genetics : BJMG · 2021Article
- BMP-2 alleviates heart failure with type 2 diabetes mellitus and doxorubicin-induced AC16 cell injury by inhibiting NLRP3 inflammasome-mediated pyroptosis.Experimental and therapeutic medicine · 2021Article
- Mechanisms Underlying Cardiomyocyte Development: Can We Exploit Them to Regenerate the Heart?Current cardiology reports · 2021Review
- Mending a broken heart:Disease models & mechanisms · 2021Review
- Transcriptional Regulation of Postnatal Cardiomyocyte Maturation and Regeneration.International journal of molecular sciences · 2021Review
- The Role ofFrontiers in cell and developmental biology · 2021Review
- Tbx20 Induction Promotes Zebrafish Heart Regeneration by Inducing Cardiomyocyte Dedifferentiation and Endocardial Expansion.Frontiers in cell and developmental biology · 2020Article
- Conservation and divergence of protein pathways in the vertebrate heart.PLoS biology · 2019Article
- Mouse HSA+ immature cardiomyocytes persist in the adult heart and expand after ischemic injury.PLoS biology · 2019Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations in T-box genes are the cause of several congenital diseases and are implicated in cancer. Tbx20-null mice exhibit severely hypoplastic hearts and express Tbx2, which is normally restricted to outflow tract and atrioventricular canal, throughout the heart. Tbx20 mutant hearts closely resemble those seen in mice overexpressing Tbx2 in myocardium, suggesting that upregulation of Tbx2 can largely account for the cardiac phenotype in Tbx20-null mice. We provide evidence that Tbx2 is a direct target for repression by Tbx20 in developing heart. We have also found that Tbx2 directly binds to the Nmyc1 promoter in developing heart, and can repress expression of the Nmyc1 promoter in transient transfection studies. Repression of Nmyc1 (N-myc) by aberrantly regulated Tbx2 can account in part for the observed cardiac hypoplasia in Tbx20 mutants. Nmyc1 is required for growth and development of multiple organs, including the heart, and overexpression of Nmyc1 is associated with childhood tumors. Despite its clinical relevance, the factors that regulate Nmyc1 expression during development are unknown. Our data present a paradigm by which T-box proteins regulate regional differences in Nmyc1 expression and proliferation to effect organ morphogenesis. We present a model whereby Tbx2 directly represses Nmyc1 in outflow tract and atrioventricular canal of the developing heart, resulting in relatively low proliferation. In chamber myocardium, Tbx20 represses Tbx2, preventing repression of Nmyc1 and resulting in relatively high proliferation. In addition to its role in regulating regional proliferation, we have found that Tbx20 regulates expression of a number of genes that specify regional identity within the heart, thereby coordinating these two important aspects of organ development.
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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.