Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration

Pengpeng Bi, John R. McAnally, John M. Shelton, Efrain Sánchez-Ortiz, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Regeneration of skeletal muscle in response to injury occurs through fusion of a population of stem cells, known as satellite cells, with injured myofibers. Myomixer, a muscle-specific membrane micropeptide, cooperates with the transmembrane protein Myomaker to regulate embryonic myoblast fusion and muscle formation. To investigate the role of Myomixer in muscle regeneration, we used CRISPR/Cas9-mediated genome editing to generate conditional knockout Myomixer alleles in mice. We show that genetic deletion of Myomixer in satellite cells using a tamoxifen-regulated Cre recombinase transgene under control of the Pax7 promoter abolishes satellite cell fusion and prevents muscle regeneration, resulting in severe muscle degeneration after injury. Satellite cells devoid of Myomixer maintain expression of Myomaker, demonstrating that Myomaker alone is insufficient to drive myoblast fusion. These findings, together with prior studies demonstrating the essentiality of Myomaker for muscle regeneration, highlight the obligatory partnership of Myomixer and Myomaker for myofiber formation throughout embryogenesis and adulthood.

Original languageEnglish (US)
Pages (from-to)3864-3869
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number15
DOIs
Publication statusPublished - Jan 1 2018

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Keywords

  • CRISPR/Cas9
  • Fusion
  • Myomaker
  • Satellite cells
  • Skeletal muscle

ASJC Scopus subject areas

  • General

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