REVIEW article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1655878
This article is part of the Research TopicElucidating the Role of Calcium Signaling in Cardiac DisordersView all 3 articles
Epicardium-Myocardium Crosstalk Orchestrates Heart Development
Provisionally accepted
Anika Nusrat
Mingfu Wu*- University of Houston, Houston, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The epicardium is critical in heart development, functioning as a paracrine signaling hub and a source of progenitor cells. Bidirectional communication between the epicardium and myocardium, mediated by tightly regulated signaling networks, is essential for proper cardiac morphogenesis. This review presents a comprehensive overview of epicardium-myocardium crosstalk across species, emphasizing how this crosstalk influences epicardial epithelial-to-mesenchymal transition (EMT), fate specification of epicardium-derived cells (EPDCs), myocardial proliferation & growth, and coronary vasculature development. We critically assess decades of research elucidating key pathways—retinoic acid, fibroblast growth factor (Fgf), insulin-like growth factor (Igf), platelet-derived growth factor (Pdgf), transforming growth factor-β (Tgfβ), various transcriptional and epigenetic regulators, as well as calcium signaling mediated epicardial function—that coordinate these developmental processes. Additionally, we include detailed tables summarizing key experimental models and mechanistic insights that have shaped the field. This integrative analysis advances our current understanding of epicardial-myocardial crosstalk and highlights unresolved questions to guide future investigations into cardiac development and disease.
Keywords: Epicardium, Myocardium, crosstalk, Morphogenesis, development
Received: 28 Jun 2025; Accepted: 10 Sep 2025.
Copyright: © 2025 Nusrat and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mingfu Wu, University of Houston, Houston, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.