Ectopic expression of Myomaker and Myomixer in slow muscle cells induces slow muscle fusion and myofiber death

Pengzheng Yong; Zhanxiong Zhang; Shaojun Du

doi:10.1016/j.jgg.2024.08.006

Volume 51 Issue 11

Nov. 2024

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Ectopic expression of Myomaker and Myomixer in slow muscle cells induces slow muscle fusion and myofiber death

doi: 10.1016/j.jgg.2024.08.006

Department of Biochemistry and Molecular Biology, Institute of Marine and Environmental Technology, University of Maryland School of Medicine, Baltimore, MD 21202, United States of America

Funds:

This work was supported by funding from the U.S. National Institute of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR072703 to S.D.).

Received Date: 2024-05-31
Accepted Date: 2024-08-21
Rev Recd Date: 2024-08-21

Available Online: 2025-06-06

Publish Date: 2024-08-30

Abstract

Abstract

Zebrafish embryos possess two major types of myofibers, the slow and fast fibers, with distinct patterns of cell fusion. The fast muscle cells can fuse, while the slow muscle cells cannot. Here, we show that myomaker is expressed in both slow and fast muscle precursors, whereas myomixer is exclusive to fast muscle cells. The loss of Prdm1a, a regulator of slow muscle differentiation, results in strong myomaker and myomixer expression and slow muscle cell fusion. This abnormal fusion is further confirmed by the direct ectopic expression of myomaker or myomixer in slow muscle cells of transgenic models. Using the transgenic models, we show that the heterologous fusion between slow and fast muscle cells can alter slow muscle cell migration and gene expression. Furthermore, the overexpression of myomaker and myomixer also disrupts membrane integrity, resulting in muscle cell death. Collectively, this study identifies that the fiber-type-specific expression of fusogenic proteins is critical for preventing inappropriate fusion between slow and fast fibers in fish embryos, highlighting the need for precise regulation of fusogenic gene expression to maintain muscle fiber integrity and specificity.
- Muscle cell fusion,
- Fiber specificity,
- Myomaker,
- Myomixer,
- Transgenic zebrafish model,
- Myofiber death

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References

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