biostudies-literatureBi PNICHD NIH HHSNIDDK NIH HHSNHLBI NIH HHSWelch FoundationNational Institutes of HealthNIAMS NIH HHS323-327https://www.ebi.ac.uk/biostudies/studies/S-EPMC5502127biostudies-literatureUnknown356(6335)Skeletal muscle formation occurs through fusion of myoblasts to form multinucleated myofibers. From a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen for genes required for myoblast fusion and myogenesis, we discovered an 84-amino acid muscle-specific peptide that we call Myomixer. Myomixer expression coincides with myoblast differentiation and is essential for fusion and skeletal muscle formation during embryogenesis. Myomixer localizes to the plasma membrane, where it promotes myoblast fusion and associates with Myomaker, a fusogenic membrane protein. Myomixer together with Myomaker can also induce fibroblast-fibroblast fusion and fibroblast-myoblast fusion. We conclude that the Myomixer-Myomaker pair controls the critical step in myofiber formation during muscle development.Science (New York, N.Y.)Control of muscle formation by the fusogenic micropeptide myomixer.PMC55021271-0025R01 AR067294R01 DK099653R01 HL130253U54 HD087351award301125award301124AR-067294, HL-130253, DK-099653, HD-087351Bassel-Duby RLi HBi PRamirez-Martinez AShelton JMCannavino JSanchez-Ortiz EOlson ENMcAnally JRfalseControl of muscle formation by the fusogenic micropeptide myomixer.Skeletal muscle formation occurs through fusion of myoblasts to form multinucleated myofibers. From a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen for genes required for myoblast fusion and myogenesis, we discovered an 84-amino acid muscle-specific peptide that we call Myomixer. Myomixer expression coincides with myoblast differentiation and is essential for fusion and skeletal muscle formation during embryogenesis. Myomixer localizes to the plasma membrane, where it promotes myoblast fusion and associates with Myomaker, a fusogenic membrane protein. Myomixer together with Myomaker can also induce fibroblast-fibroblast fusion and fibroblast-myoblast fusion. We conclude that the Myomixer-Myomaker pair controls the critical step in myofiber formation during muscle development.2017-01-01T00:00:00Z2017 Apr2024-10-17T20:15:38.069Z2019-03-27T02:49:51ZS-EPMC55021272838602410.1126/science.aam9361