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Genetic Mutations in jamb, jamc, and myomaker Revealed Different Roles on Myoblast Fusion and Muscle Growth

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Abstract

Myoblast fusion is a vital step for skeletal muscle development, growth, and regeneration. Loss of Jamb, Jamc, or Myomaker (Mymk) function impaired myoblast fusion in zebrafish embryos. In addition, mymk mutation hampered fish muscle growth. However, the effect of Jamb and Jamc deficiency on fish muscle growth is not clear. Moreover, whether jamb;jamc and jamb;mymk double mutations have stronger effects on myoblast fusion and muscle growth remains to be investigated. Here, we characterized the muscle development and growth in jamb, jamc, and mymk single and double mutants in zebrafish. We found that although myoblast fusion was compromised in jamb and jamc single or jamb;jamc double mutants, these mutant fish showed no defect in muscle cell fusion during muscle growth. The mutant fish were able to grow into adults that were indistinguishable from the wild-type sibling. In contrast, the jamb;mymk double mutants exhibited a stronger muscle phenotype compared to the jamb and jamc single and double mutants. The jamb;mymk double mutant showed reduced growth and partial lethality, similar to a mymk single mutant. Single fiber analysis of adult skeletal myofibers revealed that jamb, jamc, or jamb;jamc mutants contained mainly multinucleated myofibers, whereas jamb;mymk double mutants contained mostly mononucleated fibers. Significant intramuscular adipocyte infiltration was found in skeletal muscles of the jamb;mymk mutant. Collectively, these studies demonstrate that although Jamb, Jamc, and Mymk are all involved in myoblast fusion during early myogenesis, they have distinct roles in myoblast fusion during muscle growth. While Mymk is essential for myoblast fusion during both muscle development and growth, Jamb and Jamc are dispensable for myoblast fusion during muscle growth.

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References

  • Abmayr SM, Pavlath GK (2012) Myoblast fusion: lessons from flies and mice. Development 139:641–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Addison O, Marcus RL, LaStayo PC, Ryan AS (2014) Intermuscular fat: a review of the consequences and causes. Int J Endocrinol 2014:309570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bazzoni G (2003) The JAM family of junctional adhesion molecules. Curr Opin Cell Biol 15:525–530

    Article  CAS  PubMed  Google Scholar 

  • Bi P, Ramirez-Martinez A, Li H, Cannavino J, McAnally JR, Shelton JM, Sánchez-Ortiz E, Bassel-Duby R, Olson EN (2017) Control of muscle formation by the fusogenic micropeptide myomixer. Science 356:323–327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bi P, McAnally JR, Shelton JM, Sánchez-Ortiz E, Bassel-Duby R, Olson EN (2018) Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration. Proc Natl Acad Sci U S A 115:3864–3869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bour BA, Chakravarti M, West JM, Abmayr SM (2000) Drosophila SNS, a member of the immunoglobulin superfamily that is essential for myoblast fusion. Genes Dev 14:1498–1511

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cai M, Si Y, Zhang J, Tian Z, Du S (2018) Zebrafish embryonic slow muscle is a rapid system for genetic analysis of sarcomere organization by CRISPR/Cas9, but not NgAgo. Mar Biotechnol 20:168–181

    Article  CAS  PubMed  Google Scholar 

  • Chal J, Pourquié O (2017) Making muscle: skeletal myogenesis in vivo and in vitro. Development 144:2104–2122

    Article  CAS  PubMed  Google Scholar 

  • Chen EH, Olson EN (2004) Towards a molecular pathway for myoblast fusion in Drosophila. Trends Cell Biol 14:452–460

    Article  CAS  PubMed  Google Scholar 

  • Currie PD, Ingham PW (1996) Induction of a specific muscle cell type by a hedgehog-like protein in zebrafish. Nature 382:452–455

    Article  CAS  PubMed  Google Scholar 

  • Devoto SH, Melançon E, Eisen JS, Westerfield M (1996) Identification of separate slow and fast muscle precursor cells in vivo, prior to somite formation. Development 122:3371–3380

    CAS  PubMed  Google Scholar 

  • Di Gioia SA, Connors S, Matsunami N, Cannavino J, Rose MF, Gilette NM, Artoni P, de Macena Sobreira NL, Chan W-M, Webb BD (2017) A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nat Commun 8:16077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du SJ, Devoto SH, Westerfield M, Moon RT (1997) Positive and negative regulation of muscle cell identity by members of the hedgehog and TGF-β gene families. J Cell Biol 139:145–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du SJ, Li H, Bian Y, Zhong Y (2008) Heat-shock protein 90α1 is required for organized myofibril assembly in skeletal muscles of zebrafish embryos. Proc Natl Acad Sci 105:554–559

    Article  PubMed  Google Scholar 

  • Dulor J-P, Cambon B, Vigneron P, Reyne Y, Nouguès J, Casteilla L, Bacou F (1998) Expression of specific white adipose tissue genes in denervation-induced skeletal muscle fatty degeneration. FEBS Lett 439:89–92

    Article  CAS  PubMed  Google Scholar 

  • Dworak HA, Sink H (2002) Myoblast fusion in Drosophila. BioEssays 24:591–601

    Article  CAS  PubMed  Google Scholar 

  • Ebnet K (2017) Junctional adhesion molecules (jams): cell adhesion receptors with pleiotropic functions in cell physiology and development. Physiol Rev 97:1529–1554

    Article  CAS  PubMed  Google Scholar 

  • Ebnet K, Suzuki A, Ohno S, Vestweber D (2004) Junctional adhesion molecules (JAMs): more molecules with dual functions? J Cell Sci 117:19–29

    Article  CAS  PubMed  Google Scholar 

  • Goodpaster BH, Thaete FL, Kelley DE (2000) Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr 71:885–892

    Article  CAS  PubMed  Google Scholar 

  • Guan G, Zhang X, Naruse K, Nagahama Y, Hong Y (2014) Gene replacement by zinc finger nucleases in medaka embryos. Mar Biotechnol (NY) 16:739–747

    Article  CAS  Google Scholar 

  • Hromowyk K (2017) Genetic analysis of skeletal muscle cell fusion in zebrafish. The Ohio State University. https://etd.ohiolink.edu/pg_10?0::NO:10:P10_ACCESSION_NUM:osu1512114979019823

  • Imhof B, Zimmerli C, Gliki G, Ducrest-Gay D, Juillard P, Hammel P, Adams R, Aurrand-Lions M (2007) Pulmonary dysfunction and impaired granulocyte homeostasis result in poor survival of Jam-C-deficient mice. J Pathol 212:198–208

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Jin P, Duan R, Chen EH (2015) Mechanisms of myoblast fusion during muscle development. Curr Opin Genet Dev 32:162–170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krauss RS, Joseph GA, Goel AJ (2017) Keep your friends close: cell–cell contact and skeletal myogenesis. Cold Spring Harb Perspect Biol 9(2):a029298. https://doi.org/10.1101/cshperspect.a029298

    Article  PubMed  PubMed Central  Google Scholar 

  • Landemaine A, Rescan P-Y, Gabillard J-C (2014) Myomaker mediates fusion of fast myocytes in zebrafish embryos. Biochem Biophys Res Commun 451:480–484

    Article  CAS  PubMed  Google Scholar 

  • Li H, Zhong Y, Wang Z, Gao J, Xu J, Chu W, Zhang J, Fang S, Du SJ (2013) Smyd1b is required for skeletal and cardiac muscle function in zebrafish. Mol Biol Cell 24:3511–3521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Pei W, Vergarajauregui S, Zerfas PM, Raben N, Burgess SM, Puertollano R (2017) Novel degenerative and developmental defects in a zebrafish model of mucolipidosis type IV. Hum Mol Genet 26:2701–2718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo W, Li E, Nie Q, Zhang X (2015) Myomaker, regulated by MYOD, MYOG and miR-140-3p, promotes chicken myoblast fusion. Int J Mol Sci 16:26186–26201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manini TM, Clark BC, Nalls MA, Goodpaster BH, Ploutz-Snyder LL, Harris TB (2007) Reduced physical activity increases intermuscular adipose tissue in healthy young adults. Am J Clin Nutr 85:377–384

    Article  CAS  PubMed  Google Scholar 

  • Millay DP, O’Rourke JR, Sutherland LB, Bezprozvannaya S, Shelton JM, Bassel-Duby R, Olson EN (2013) Myomaker is a membrane activator of myoblast fusion and muscle formation. Nature 499:301–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Millay DP, Sutherland LB, Bassel-Duby R, Olson EN (2014) Myomaker is essential for muscle regeneration. Genes Dev 28:1641–1646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Powell GT, Wright GJ (2011) Jamb and jamc are essential for vertebrate myocyte fusion. PLoS Biol 9:e1001216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Praetor A, McBride JM, Chiu H, Rangell L, Cabote L, Lee WP, Cupp J, Danilenko DM, Fong S (2009) Genetic deletion of JAM-C reveals a role in myeloid progenitor generation. Blood 113:1919–1928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiu C, Cheng B, Zhang Y, Huang R, Liao L, Li Y, Luo D, Hu W, Wang Y (2014) Efficient knockout of transplanted green fluorescent protein gene in medaka using TALENs. Mar Biotechnol (NY) 16:674–683

    Article  CAS  Google Scholar 

  • Quinn ME, Goh Q, Kurosaka M, Gamage DG, Petrany MJ, Prasad V, Millay DP (2017) Myomerger induces fusion of non-fusogenic cells and is required for skeletal muscle development. Nat Commun 8:15665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rochlin K, Yu S, Roy S, Baylies MK (2010) Myoblast fusion: when it takes more to make one. Dev Biol 341:66–83

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Gómez M, Coutts N, Price A, Taylor MV, Bate M (2000) Drosophila dumbfounded: a myoblast attractant essential for fusion. Cell 102:189–198

    Article  PubMed  Google Scholar 

  • Sampath SC, Sampath SC, Millay DP (2018) Myoblast fusion confusion: the resolution begins. Skelet Muscle 8:3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheiermann C, Meda P, Aurrand-Lions M, Madani R, Yiangou Y, Coffey P, Salt TE, Ducrest-Gay D, Caille D, Howell O (2007) Expression and function of junctional adhesion molecule-C in myelinated peripheral nerves. Science 318:1472–1475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi J, Bi P, Pei J, Li H, Grishin NV, Bassel-Duby R, Chen EH, Olson EN (2017) Requirement of the fusogenic micropeptide myomixer for muscle formation in zebrafish. Proc Natl Acad Sci U S A 114:11950–11955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi J, Cai M, Si Y, Zhang J, Du S (2018) Knockout of myomaker results in defective myoblast fusion, reduced muscle growth and increased adipocyte infiltration in zebrafish skeletal muscle. Hum Mol Genet 27:3542–3554

    Article  CAS  PubMed  Google Scholar 

  • Srinivas BP, Woo J, Leong WY, Roy S (2007) A conserved molecular pathway mediates myoblast fusion in insects and vertebrates. Nat Genet 39:781–786

    Article  CAS  PubMed  Google Scholar 

  • Strünkelnberg M, Bonengel B, Moda LM, Hertenstein A, de Couet HG, Ramos RG, Fischbach K-F (2001) rst and its paralogue kirre act redundantly during embryonic muscle development in Drosophila. Development 128:4229–4239

    PubMed  Google Scholar 

  • Tan X, Rotllant J, Li H, DeDeyne P, Du SJ (2006) SmyD1, a histone methyltransferase, is required for myofibril organization and muscle contraction in zebrafish embryos. Proc Natl Acad Sci U S A 103:2713–2718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams AF, Barclay AN (1988) The immunoglobulin superfamily—domains for cell surface recognition. Annu Rev Immunol 6:381–405

    Article  CAS  Google Scholar 

  • Xu J, Gao J, Li J, Xue L, Clark KJ, Ekker SC, Du SJ (2012) Functional analysis of slow myosin heavy chain 1 and myomesin-3 in sarcomere organization in zebrafish embryonic slow muscles. J Genet Genomics 39:69–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye M, Hamzeh R, Geddis A, Varki N, Perryman MB, Grossfeld P (2009) Deletion of JAM-C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice. Am J Med Genet A 149A:1438–1443

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Roy S (2017) Myomaker is required for the fusion of fast-twitch myocytes in the zebrafish embryo. Dev Biol 423:24–33

    Article  CAS  PubMed  Google Scholar 

  • Zhang Q, Vashisht AA, O’Rourke J, Corbel SY, Moran R, Romero A, Miraglia L, Zhang J, Durrant E, Schmedt C (2017) The microprotein minion controls cell fusion and muscle formation. Nat Commun 8:15664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

YS is supported by fellowships from the Chinese Scholarship Council. We thank Sharon L. Amacher for sharing the information that similar work has been carried out in her laboratory in zebrafish mymk and jam mutants prior to submission for publication.

Funding

This research was supported by a seed funding from University of Maryland and a grant from the National Institute of Health to SD (1R01AR072703-01A1).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Institute of Marine and Environmental Technology, University of Maryland School of Medicine, 701 East Pratt Street, Baltimore, MD, 21202, USA

    Yufeng Si & Shaojun Du

  2. The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, China

    Yufeng Si & Haishen Wen

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  1. Yufeng Si
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Correspondence to Shaojun Du.

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All animal studies were carried out in accordance with the guideline for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Institutional Animal Care and Use Committee of the University of Maryland (Permit Number 0516005).

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The authors declare that they have no conflict of interest.

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Si, Y., Wen, H. & Du, S. Genetic Mutations in jamb, jamc, and myomaker Revealed Different Roles on Myoblast Fusion and Muscle Growth. Mar Biotechnol 21, 111–123 (2019). https://doi.org/10.1007/s10126-018-9865-x

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