ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Embryonic Development
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1636944
Smarce1 fine-tunes Cardiomyocyte Proliferation in the Embryonic Zebrafish Heart
Provisionally accepted
- 1Universitat Ulm, Ulm, Germany
- 2Ulm University Medical Center, Ulm, Germany
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Signaling pathways that govern organ growth during embryonic development are frequently reactivated in adult tissues to support regenerative processes. Despite their therapeutic relevance for cardiac repair, the molecular mechanisms regulating heart growth during development and regeneration remain incompletely understood. In this study, we identified the zebrafish mutant heart of stone (hos) in an ENU mutagenesis screen, which exhibits markedly increased cardiac growth driven by excessive cardiomyocyte proliferation, independent of hypertrophic mechanisms.Through forward and reverse genetics approaches, we determined that the hos phenotype arises from loss of function in smarce1, a core component of the SWI/SNF chromatin remodeling complex. Strikingly, inducible, myocardium-specific overexpression of smarce1 during development attenuated cardiomyocyte proliferation, indicating that Smarce1 acts as a cell-autonomous molecular switch that fine-tunes proliferative capacity in the developing heart.Together, our findings reveal Smarce1 as a key regulator of cardiomyocyte proliferation during zebrafish heart development and implicate chromatin remodeling via SWI/SNF as a critical mechanism controlling cardiac growth.
Keywords: cardiomyocyte, proliferation, SMARCE1, SWI/SNF complex, Zebrafish
Received: 28 May 2025; Accepted: 04 Jul 2025.
Copyright: © 2025 Park, Dahme, Krieg, Just and Rottbauer. 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:
Steffen Just, Universitat Ulm, Ulm, Germany
Wolfgang Rottbauer, Ulm University Medical Center, Ulm, Germany
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