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The relationship between muscle stem cells and motor neurons

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Abstract

Neuromuscular system is constituted of multi-fibrillar muscles, tendons, motor neurons and associated muscle stem cells. Stereotyped pattern of muscle innervation and muscle-specific interactions with tendon cells suggest that neuromuscular system develops in a coordinated way. Remarkably, upon regeneration, coordinated assembly of all neuromuscular components is also critical to rebuild functional muscle. Thus, to ensure muscle function, the neuromuscular system components need to interact both during development and regeneration. Over the last decades, interactions between muscles and tendons, muscles and motor neurons and between muscles and muscle stem cells have been extensively analysed and documented. However, only recent evidence indicates that muscle stem cells interact with motor neurons and that these interactions contribute to building functional muscle both during development and regeneration. From this perspective, we discuss here the relationship between muscle stem cells and motor neurons during Drosophila neuromuscular system development and adverse impact of affected muscle stem cell–motor neuron interactions in regenerating vertebrate muscle.

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References

  1. Lavergne G, Zmojdzian M, Da Ponte JP et al (2020) Drosophila adult muscle precursor cells contribute to motor axon pathfinding and proper innervation of embryonic muscles. Development 147(4):183004

    Article  Google Scholar 

  2. Ruiz Gómez M, Bate M (1997) Segregation of myogenic lineages in Drosophila requires numb. Development 124:4857–4866

    Article  Google Scholar 

  3. Figeac N, Daczewska M, Marcelle C, Jagla K (2007) Muscle stem cells and model systems for their investigation. Dev Dyn 236:3332–3342

    Article  Google Scholar 

  4. Aradhya R, Zmojdzian M, Da Ponte JP, Jagla K (2015) Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila. Elife 4:e08497

    Article  Google Scholar 

  5. Figeac N, Jagla T, Aradhya R et al (2010) Drosophila adult muscle precursors form a network of interconnected cells and are specified by the rhomboid-triggered EGF pathway. Development 137:1965–1973

    Article  CAS  Google Scholar 

  6. Chaturvedi D, Reichert H, Gunage RD, VijayRaghavan K (2017) Identification and functional characterization of muscle satellite cells in Drosophila. Elife 6:e30107

    Article  Google Scholar 

  7. Boukhatmi H, Bray S (2018) A population of adult satellite-like cells in Drosophila is maintained through a switch in RNA-isoforms. Elife 7:e35954

    Article  Google Scholar 

  8. Tixier V, Bataillé L, Jagla K (2010) Diversification of muscle types: Recent insights from Drosophila. Exp Cell Res 316:3019–3027

    Article  CAS  Google Scholar 

  9. Bate M, Rushton E, Currie DA (1991) Cells with persistent twist expression are the embryonic precursors of adult muscles in Drosophila. Development 113:79–89

    Article  CAS  Google Scholar 

  10. Liotta D, Han J, Elgar S et al (2007) The Him gene reveals a balance of inputs controlling muscle differentiation in Drosophila. Curr Biol 17:1409–1413

    Article  CAS  Google Scholar 

  11. Postigo AA, Ward E, Skeath JB, Dean DC (1999) zfh-1, the Drosophila homologue of ZEB, is a transcriptional repressor that regulates somatic myogenesis. Mol Cell Biol 19:7255–7263

    Article  CAS  Google Scholar 

  12. Mourikis P, Sambasivan R, Castel D et al (2012) A critical requirement for notch signaling in maintenance of the quiescent skeletal muscle stem cell state. Stem Cells 3:243–252

    Article  Google Scholar 

  13. Noguchi YT, Nakamura M, Hino N et al (2019) Cell-autonomous and redundant roles of Hey1 and HeyL in muscle stem cells: HeyL requires Hes1 to bind diverse DNA sites. Development. https://doi.org/10.1242/dev.163618

    Article  PubMed  Google Scholar 

  14. Fujimaki S, Seko D, Kitajima Y et al (2018) Notch1 and Notch2 coordinately regulate stem cell function in the quiescent and activated states of muscle satellite cells. Stem Cells 36:278–285

    Article  CAS  Google Scholar 

  15. Aradhya R, Jagla K (2020) Insulin-dependent non-canonical activation of notch in Drosophila: A story of notch-induced muscle stem cell proliferation. Adv Exp Med Biol 1227:131–144

    Article  CAS  Google Scholar 

  16. Farrell ER, Keshishian H (1999) Laser ablation of persistent twist cells in Drosophila: muscle precursor fate is not segmentally restricted. Development 126:273–280

    Article  CAS  Google Scholar 

  17. Dutta D, Shaw S, Maqbool T et al (2005) Drosophila Heartless acts with Heartbroken/Dof in muscle founder differentiation. PLoS Biol 3:e337

    Article  Google Scholar 

  18. Siles L, Ninfali C, Cortés M et al (2019) ZEB1 protects skeletal muscle from damage and is required for its regeneration. Nat Commun 10:1364

    Article  Google Scholar 

  19. Buckingham M, Relaix F (2007) The role of Pax genes in the development of tissues and organs: Pax3 and Pax7 regulate muscle progenitor cell functions. Annu Rev Cell Dev Biol 23:645–673

    Article  CAS  Google Scholar 

  20. Feige P, Brun CE, Ritso M, Rudnicki MA (2018) Orienting muscle stem cells for regeneration in homeostasis, aging, and disease. Cell Stem Cell 23:653–664

    Article  CAS  Google Scholar 

  21. De Micheli AJ, Laurilliard EJ, Heinke CL et al (2020) Single-cell analysis of the muscle stem cell hierarchy identifies heterotypic communication signals involved in skeletal muscle regeneration. Cell Rep 30:3583-3595.e5

    Article  Google Scholar 

  22. Dos Santos M, Backer S, Saintpierre B et al (2020) Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers. Nat Commun 11:5102

    Article  Google Scholar 

  23. Petrany MJ, Swoboda CO, Sun C et al (2020) Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers. Nat Commun 11:6374

    Article  CAS  Google Scholar 

  24. Rocheteau P, Gayraud-Morel B, Siegl-Cachedenier I et al (2012) A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division. Cell 148:112–125

    Article  CAS  Google Scholar 

  25. Liu W, Wei-LaPierre L, Klose A et al (2015) Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions. Elife 4:e09221

    Article  Google Scholar 

  26. Liu W, Klose A, Forman S et al (2017) Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration. Elife 6:e26464

    Article  Google Scholar 

  27. Wong A, Garcia SM, Tamaki S et al (2021) Satellite cell activation and retention of muscle regenerative potential after long-term denervation. Stem Cells 39:331–344

    Article  CAS  Google Scholar 

  28. Frugier T, Nicole S, Cifuentes-Diaz C, Melki J (2002) The molecular bases of spinal muscular atrophy. Curr Opin Genet Dev 12:294–298

    Article  CAS  Google Scholar 

  29. Nicole S, Desforges B, Millet G et al (2003) Intact satellite cells lead to remarkable protection against Smn gene defect in differentiated skeletal muscle. J Cell Biol 161:571–582

    Article  CAS  Google Scholar 

  30. Guettier-Sigrist S, Hugel B, Coupin G et al (2002) Possible pathogenic role of muscle cell dysfunction in motor neuron death in spinal muscular atrophy. Muscle Nerve 25:700–708

    Article  Google Scholar 

  31. Liu N, Glynnis A, Garry A et al (2017) Twist2-dependent progenitor cell contributes to adult skeletal muscle. Nat Cell Biol 19:202–213

    Article  CAS  Google Scholar 

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Acknowledgements

This work was funded by strategic grant of AFM-Telethon to MyoNeurAlp aliance (MZ and KJ) and by the iSITE CAP20-25 grant to MZ.

Funding

This work was supported by the iSITE CAP20-25 grant and the strategic AFM-Téléthon grant to MyoNeurAlp consortium.

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KJ conceptualised the manuscript, MZ and KJ wrote the manuscript.

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Correspondence to Krzysztof Jagla.

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Zmojdzian, M., Jagla, K. The relationship between muscle stem cells and motor neurons. Cell. Mol. Life Sci. 78, 5043–5049 (2021). https://doi.org/10.1007/s00018-021-03838-2

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  • DOI: https://doi.org/10.1007/s00018-021-03838-2

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