ArticleDevelopment (Cambridge, England)2012
Nf1 limits epicardial derivative expansion by regulating epithelial to mesenchymal transition and proliferation.
Article in Development (Cambridge, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- The RNA-binding protein SRSF3 controls epicardial formation by regulating splicing and proliferation.Development (Cambridge, England) · 2026Article
- Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025Review
- Molecular convergence of risk variants for congenital heart defects leveraging a regulatory map of the human fetal heart.medRxiv : the preprint server for health sciences · 2024Article
- EZH2 controls epicardial cell migration during heart development.Life science alliance · 2023Article
- The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells.Nature communications · 2022Article
- The landscape of accessible chromatin in quiescent cardiac fibroblasts and cardiac fibroblasts activated after myocardial infarction.Epigenetics · 2022Article
- Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling.BMC neurology · 2021Article
- Developmental Pathways of Cardiac Fibroblasts.Cold Spring Harbor perspectives in biology · 2020Review
- Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair.Pharmacology & therapeutics · 2020Review
- An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque?F1000Research · 2018Review
- More than Just a Simple Cardiac Envelope; Cellular Contributions of the Epicardium.Frontiers in cell and developmental biology · 2017Review
- Defining the Cardiac Fibroblast.Circulation journal : official journal of the Japanese Circulation Society · 2016Review
- Genetic tools for identifying and manipulating fibroblasts in the mouse.Differentiation; research in biological diversity · 2016Review
- Epicardial Outgrowth Culture Assay and Ex Vivo Assessment of Epicardial-derived Cell Migration.Journal of visualized experiments : JoVE · 2016Article
- Crim1 has cell-autonomous and paracrine roles during embryonic heart development.Scientific reports · 2016Article
- Tbx5 is required for avian and Mammalian epicardial formation and coronary vasculogenesis.Circulation research · 2014Article
- The Epicardium and the Development of the Atrioventricular Junction in the Murine Heart.Journal of developmental biology · 2014Article
- Mice carrying a hypomorphic Evi1 allele are embryonic viable but exhibit severe congenital heart defects.PloS one · 2014Article
- Tbx18 regulates development of the epicardium and coronary vessels.Developmental biology · 2013Article
- Snai1 is important for avian epicardial cell transformation and motility.Developmental dynamics : an official publication of the American Association of Anatomists · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The epicardium is the primary source of coronary vascular smooth muscle cells (cVSMCs) and fibroblasts that reside in the compact myocardium. To form these epicardial-derived cells (EPDCs), the epicardium undergoes the process of epithelial to mesenchymal transition (EMT). Although several signaling pathways have been identified that disrupt EMT, no pathway has been reported that restricts this developmental process. Here, we identify neurofibromin 1 (Nf1) as a key mediator of epicardial EMT. To determine the function of Nf1 during epicardial EMT and the formation of epicardial derivatives, cardiac fibroblasts and cVSMCs, we generated mice with a tissue-specific deletion of Nf1 in the epicardium. We found that mutant epicardial cells transitioned more readily to mesenchymal cells in vitro and in vivo. The mesothelial epicardium lost epithelial gene expression and became more invasive. Using lineage tracing of EPDCs, we found that the process of EMT occurred earlier in Nf1 mutant hearts, with an increase in epicardial cells entering the compact myocardium. Moreover, loss of Nf1 caused increased EPDC proliferation and resulted in more cardiac fibroblasts and cVSMCs. Finally, we were able to partially reverse the excessive EMT caused by loss of Nf1 by disrupting Pdgfrα expression in the epicardium. Conversely, Nf1 activation was able to inhibit PDGF-induced epicardial EMT. Our results demonstrate a regulatory role for Nf1 during epicardial EMT and provide insights into the susceptibility of patients with disrupted NF1 signaling to cardiovascular disease.
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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.