Loss of Myomixer Results in Defective Myoblast Fusion, Impaired Muscle Growth, and Severe Myopathy in Zebrafish

Ping Wu, Pengzheng Yong, Zhanxiong Zhang, Rui Xu, Renjie Shang, Jun Shi, Jianshe Zhang, Pengpeng Bi, Elizabeth Chen, Shaojun Du

Research output: Contribution to journalLetterpeer-review

3 Scopus citations

Abstract

The development and growth of fish skeletal muscles require myoblast fusion to generate multinucleated myofibers. While zebrafish fast-twitch muscle can fuse to generate multinucleated fibers, the slow-twitch muscle fibers remain mononucleated in zebrafish embryos and larvae. The mechanism underlying the fiber-type-specific control of fusion remains elusive. Recent genetic studies using mice identified a long-sought fusion factor named Myomixer. To understand whether Myomixer is involved in the fiber-type specific fusion, we analyzed the transcriptional regulation of myomixer expression and characterized the muscle growth phenotype upon genetic deletion of myomixer in zebrafish. The data revealed that overexpression of Sonic Hedgehog (Shh) drastically inhibited myomixer expression and blocked myoblast fusion, recapitulating the phenotype upon direct genetic deletion of myomixer from zebrafish. The fusion defect in myomixer mutant embryos could be faithfully rescued upon re-expression of zebrafish myomixer gene or its orthologs from shark or human. Interestingly, myomixer mutant fish survived to adult stage though were notably smaller than wildtype siblings. Severe myopathy accompanied by the uncontrolled adipose infiltration was observed in both fast and slow muscle tissues of adult myomixer mutants. Collectively, our data highlight an indispensable role of myomixer gene for cell fusion during both embryonic muscle development and post-larval muscle growth.

Original languageEnglish (US)
Pages (from-to)1023-1038
Number of pages16
JournalMarine Biotechnology
Volume24
Issue number5
DOIs
StatePublished - Oct 2022

Keywords

  • Hedgehog
  • Myoblast fusion
  • Myomixer
  • Zebrafish

ASJC Scopus subject areas

  • Biotechnology
  • Aquatic Science

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