ArticleScientific reports2016
Irx3 is required for postnatal maturation of the mouse ventricular conduction system.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation.Frontiers in cardiovascular medicine · 2022Pooled it
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Article
- Multifaceted role of Iroquois signaling in development and diseases.Molecules and cells · 2025Review
- 3D imaging and single-cell analysis reveal cellular heterogeneity of lymphatic valve endothelial cell types.iScience · 2025Article
- Cardiac Development, Cellular Composition and Function: From Regulatory Mechanisms to Applications.Cells · 2025Review
- SHP2 genetic variants in NSML-associated RASopathies disrupt the PZR-IRX transcription factor signaling axis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- IRX3 controls a SUMOylation-dependent differentiation switch in adipocyte precursor cells.Nature communications · 2025Article
- Immune-mediated cardiac development and regeneration.Seminars in cell & developmental biology · 2025Review
- Cardiac differentiation roadmap for analysis of plasticity and balanced lineage commitment.Stem cell reports · 2025Article
- Single-Cell Transcriptomics Identified Fibrosis-Activated Valve Interstitial Cells Involved in Functional Tricuspid Regurgitation.JACC. Asia · 2025Article
- Single-cell multi-modal integrative analyses highlight functional dynamic gene regulatory networks directing human cardiac development.Cell genomics · 2024Article
- Transcriptional regulation of the postnatal cardiac conduction system heterogeneity.Nature communications · 2024Article
- Improving iPSC Differentiation Using a Nanodot Platform.ACS applied materials & interfaces · 2024Article
- Complementary and Inducible creERStem cell reviews and reports · 2024Article
- Development of the Cardiac Conduction System.Advances in experimental medicine and biology · 2024Article
- Advances and Prospects in Understanding Vertebrate Cardiac Conduction System, Pacemaker Cell, and Cardiac Muscle Development: Toward Novel Biological Therapies.Muscles (Basel, Switzerland) · 2023Review
- Low levels of circulating methylated IRX3 are related to worse outcome after transcatheter aortic valve implantation in patients with severe aortic stenosis.Clinical epigenetics · 2023Article
- Article
- Cardiac copper content and its relationship with heart physiology: Insights based on quantitative genetic and functional analyses using BXD family mice.Frontiers in cardiovascular medicine · 2023Article
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9 authors at 5 institutions in 1 country.
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Abstract
The ventricular conduction system (VCS) orchestrates the harmonious contraction in every heartbeat. Defects in the VCS are often associated with life-threatening arrhythmias and also promote adverse remodeling in heart disease. We have previously established that the Irx3 homeobox gene regulates rapid electrical propagation in the VCS by modulating the transcription of gap junction proteins Cx40 and Cx43. However, it is unknown whether other factors contribute to the conduction defects observed in Irx3 knockout (Irx3(-/-)) mice. In this study, we show that during the early postnatal period, Irx3(-/-) mice develop morphological defects in the VCS which are temporally dissociated from changes in gap junction expression. These morphological defects were accompanied with progressive changes in the cardiac electrocardiogram including right bundle branch block. Hypoplastic VCS was not associated with increased apoptosis of VCS cardiomyocytes but with a lack of recruitment and maturation of ventricular cardiomyocytes into the VCS. Computational analysis followed by functional verification revealed that Irx3 promotes VCS-enriched transcripts targeted by Nkx2.5 and/or Tbx5. Altogether, these results indicate that, in addition to ensuring the appropriate expression of gap junctional channels in the VCS, Irx3 is necessary for the postnatal maturation of the VCS, possibly via its interactions with Tbx5 and Nkx2.5.
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