ArticleDevelopment (Cambridge, England)2021
The extracellular matrix protein agrin is essential for epicardial epithelial-to-mesenchymal transition during heart development.
Article in Development (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Role of Agrin in tissue repair and regeneration: From mechanisms to therapeutic opportunities (Review).International journal of molecular medicine · 2024Pooled it
- O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2026Review
- Cell-free strategies for cardiomyocyte proliferation and heart repair.Pharmacological reports : PR · 2026Review
- Revealing the complexity of the epicardial secretome.Scientific reports · 2025Article
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025Review
- Decoding congenital heart disease: a multi-omic framework for cardiac lineage and regulatory dysfunction.Frontiers in cell and developmental biology · 2025Review
- Protein glycosylation in cardiovascular health and disease.Nature reviews. Cardiology · 2024Review
- Epicardial EMT and cardiac repair: an update.Stem cell research & therapy · 2024Review
- Exploring the Function of Epicardial Cells Beyond the Surface.Circulation research · 2024Review
- Review
- Epicardium and Coronary Vessels.Advances in experimental medicine and biology · 2024Review
- Understanding Epicardial Cell Heterogeneity during Cardiogenesis and Heart Regeneration.Journal of cardiovascular development and disease · 2023Review
- EZH2 controls epicardial cell migration during heart development.Life science alliance · 2023Article
- Mechanobiology: A landscape for reinterpreting stem cell heterogeneity and regenerative potential in diseased tissues.iScience · 2023Review
- Actin polymerization and depolymerization in developing vertebrates.Frontiers in physiology · 2023Review
- Bioinformatics-based analysis of the roles of basement membrane-related gene AGRN in systemic lupus erythematosus and pan-cancer development.Frontiers in immunology · 2023Article
- CCBE1 Is Essential for Epicardial Function during Myocardium Development.International journal of molecular sciences · 2022Article
- Manipulating Cardiomyocyte Plasticity for Heart Regeneration.Frontiers in cell and developmental biology · 2022Review
- Determination of Agrin and Related Proteins Levels as a Function of Age in Human Hearts.Frontiers in cardiovascular medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
During heart development, epicardial cells residing within the outer layer undergo epithelial-mesenchymal transition (EMT) and migrate into the underlying myocardium to support organ growth and morphogenesis. Disruption of epicardial EMT results in embryonic lethality, yet its regulation is poorly understood. Here, we report epicardial EMT within the mesothelial layer of the mouse embryonic heart at ultra-high resolution using scanning electron microscopy combined with immunofluorescence analyses. We identified morphologically active EMT regions that associated with key components of the extracellular matrix, including the basement membrane-associated proteoglycan agrin. Deletion of agrin resulted in impaired EMT and compromised development of the epicardium, accompanied by downregulation of Wilms' tumor 1. Agrin enhanced EMT in human embryonic stem cell-derived epicardial-like cells by decreasing β-catenin and promoting pFAK localization at focal adhesions, and promoted the aggregation of dystroglycan within the Golgi apparatus in murine epicardial cells. Loss of agrin resulted in dispersal of dystroglycan in vivo, disrupting basement membrane integrity and impairing EMT. Our results provide new insights into the role of the extracellular matrix in heart development and implicate agrin as a crucial regulator of epicardial EMT.
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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.