ArticleDisease models & mechanisms2023
The developing epicardium regulates cardiac chamber morphogenesis by promoting cardiomyocyte growth.
Article in Disease models & mechanisms, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Nr2f1a and Isl1 repress acquisition of epicardial identity in venous atrial cardiomyocytes.Development (Cambridge, England) · 2026Article
- Adgrg6/Gpr126 is required for compact wall integrity and establishing trabecular identity during cardiac trabeculation.Nature communications · 2026Article
- Epicardial Tcf21 facilitates cardiomyocyte dedifferentiation and heart regeneration in zebrafish.Developmental biology · 2026Article
- Invasion of Epicardial-Derived Cells to the Trabeculae Mediated by NFPs-Fgf Signaling Regulates Ventricular Compaction.Circulation. Heart failure · 2026Article
- Article
- Revealing the complexity of the epicardial secretome.Scientific reports · 2025Article
- The pericardium forms as a distinct structure during heart formation.Nature communications · 2025Article
- A systems genetics approach identifies roles for proteasome factors in heart development and congenital heart defects.PLoS genetics · 2025Article
- A zebrafish model of nicotinamide adenine dinucleotide (NADbioRxiv : the preprint server for biology · 2025Article
- Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025Review
- morphoHeart: A quantitative tool for integrated 3D morphometric analyses of heart and ECM during embryonic development.PLoS biology · 2025Article
- Enhanced neoangiogenesis and balance of the immune response mediated by the Wilms' tumor suppressor WT1 favor repair after myocardial infarction.Theranostics · 2025Article
- Distinct mechanisms regulate ventricular and atrial chamber wall formation.Nature communications · 2024Article
- Exploring the Function of Epicardial Cells Beyond the Surface.Circulation research · 2024Review
- Llgl1 mediates timely epicardial emergence and establishment of an apical laminin sheath around the trabeculating cardiac ventricle.Development (Cambridge, England) · 2024Article
- Article
- Novel Insights into the Molecular Mechanisms Governing Embryonic Epicardium Formation.Journal of cardiovascular development and disease · 2023Review
- Review
- From mechanisms of heart failure to clinical heart success.Disease models & mechanisms · 2023Article
- Cardiomyocyte-fibroblast crosstalk in the postnatal heart.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The epicardium, the outermost layer of the heart, is an important regulator of cardiac regeneration. However, a detailed understanding of the crosstalk between the epicardium and myocardium during development requires further investigation. Here, we generated three models of epicardial impairment in zebrafish by mutating the transcription factor genes tcf21 and wt1a, and ablating tcf21+ epicardial cells. Notably, all three epicardial impairment models exhibited smaller ventricles. We identified the initial cause of this phenotype as defective cardiomyocyte growth, resulting in reduced cell surface and volume. This failure of cardiomyocyte growth was followed by decreased proliferation and increased abluminal extrusion. By temporally manipulating its ablation, we show that the epicardium is required to support cardiomyocyte growth mainly during early cardiac morphogenesis. By transcriptomic profiling of sorted epicardial cells, we identified reduced expression of FGF and VEGF ligand genes in tcf21-/- hearts, and pharmacological inhibition of these signaling pathways in wild type partially recapitulated the ventricular growth defects. Taken together, these data reveal distinct roles of the epicardium during cardiac morphogenesis and signaling pathways underlying epicardial-myocardial crosstalk.
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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.