Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

A Pax3/Pax7-dependent population of skeletal muscle progenitor cells

Nature volume 435, pages 948–953 (2005)Cite this article

Abstract

During vertebrate development, successive phases of embryonic and fetal myogenesis lead to the formation and growth of skeletal muscles1. Although the origin and molecular regulation of the earliest embryonic muscle cells is well understood2, less is known about later stages of myogenesis. We have identified a new cell population that expresses the transcription factors Pax3 and Pax7 (paired box proteins 3 and 7) but no skeletal-muscle-specific markers. These cells are maintained as a proliferating population in embryonic and fetal muscles of the trunk and limbs throughout development. Using a stable green fluorescent protein (GFP) reporter targeted to Pax3, we demonstrate that they constitute resident muscle progenitor cells that subsequently become myogenic and form skeletal muscle. Late in fetal development, these cells adopt a satellite cell position characteristic of progenitor cells in postnatal muscle. In the absence of both Pax3 and Pax7, further muscle development is arrested and only the early embryonic muscle of the myotome forms. Cells failing to express Pax3 or Pax7 die or assume a non-myogenic fate. We conclude that this resident Pax3/Pax7-dependent progenitor cell population constitutes a source of myogenic cells of prime importance for skeletal muscle formation, a finding also of potential value in the context of cell therapy for muscle disease.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Pax7 and Pax3 label a distinct cell population present in embryonic skeletal muscle.
Figure 2: Pax3+Pax7+ cells contribute to skeletal muscle.
Figure 3: Pax3+Pax7+ progenitors adopt a satellite cell position from late fetal stages.
Figure 4: Major myogenic defects in Pax3/Pax7 double mutant embryos.

Similar content being viewed by others

References

  1. Cossu, G. in Advances in Developmental Biology and Biochemistry (ed. Wassarman, P. M.) 127–142 (Elsevier, San Diego, 2001)

    Google Scholar 

  2. Pownall, M. E., Gustafsson, M. K. & Emerson, C. P. Jr Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Annu. Rev. Cell Dev. Biol. 18, 747–783 (2002)

    Article  CAS  Google Scholar 

  3. Tremblay, P. et al. A crucial role for Pax3 in the development of the hypaxial musculature and the long-range migration of muscle precursors. Dev. Biol. 203, 49–61 (1998)

    Article  CAS  Google Scholar 

  4. Borycki, A. G., Li, J., Jin, F., Emerson, C. P. & Epstein, J. A. Pax3 functions in cell survival and in pax7 regulation. Development 126, 1665–1674 (1999)

    CAS  Google Scholar 

  5. Buckingham, M. et al. The formation of skeletal muscle: from somite to limb. J. Anat. 202, 59–68 (2003)

    Article  Google Scholar 

  6. Tajbakhsh, S., Rocancourt, D., Cossu, G. & Buckingham, M. Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and Myf-5 act upstream of MyoD. Cell 89, 127–138 (1997)

    Article  CAS  Google Scholar 

  7. Kassar-Duchossoy, L. et al. Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice. Nature 431, 466–471 (2004)

    Article  ADS  CAS  Google Scholar 

  8. Rudnicki, M. A. et al. MyoD or Myf-5 is required for the formation of skeletal muscle. Cell 75, 1351–1359 (1993)

    Article  CAS  Google Scholar 

  9. Relaix, F., Rocancourt, D., Mansouri, A. & Buckingham, M. Divergent functions of murine Pax3 and Pax7 in limb muscle development. Genes Dev. 18, 1088–1105 (2004)

    Article  CAS  Google Scholar 

  10. Seale, P. et al. Pax7 is required for the specification of myogenic satellite cells. Cell 102, 777–786 (2000)

    Article  CAS  Google Scholar 

  11. Oustanina, S., Hause, G. & Braun, T. Pax7 directs postnatal renewal and propagation of myogenic satellite cells but not their specification. EMBO J. 23, 3430–3439 (2004)

    Article  CAS  Google Scholar 

  12. Schubert, F. R. et al. Early mesodermal phenotypes in splotch suggest a role for Pax3 in the formation of epithelial somites. Dev. Dyn. 222, 506–521 (2001)

    Article  CAS  Google Scholar 

  13. Williams, B. A. & Ordahl, C. P. Pax-3 expression in segmental mesoderm marks early stages in myogenic cell specification. Development 120, 785–796 (1994)

    CAS  Google Scholar 

  14. Bober, E., Franz, T., Arnold, H. H., Gruss, P. & Tremblay, P. Pax-3 is required for the development of limb muscles: a possible role for the migration of dermomyotomal muscle progenitor cells. Development 120, 603–612 (1994)

    CAS  Google Scholar 

  15. Goulding, M., Lumsden, A. & Paquette, A. J. Regulation of Pax-3 expression in the dermomyotome and its role in muscle development. Development 120, 957–971 (1994)

    CAS  Google Scholar 

  16. Tajbakhsh, S. & Buckingham, M. The birth of muscle progenitor cells in the mouse: spatiotemporal considerations. Curr. Top. Dev. Biol. 48, 225–268 (2000)

    Article  CAS  Google Scholar 

  17. Jostes, B., Walther, C. & Gruss, P. The murine paired box gene, Pax7, is expressed specifically during the development of the nervous and muscular system. Mech. Dev. 33, 27–37 (1990)

    Article  CAS  Google Scholar 

  18. Mansouri, A., Stoykova, A., Torres, M. & Gruss, P. Dysgenesis of cephalic neural crest derivatives in Pax7-/- mutant mice. Development 122, 831–838 (1996)

    CAS  Google Scholar 

  19. Kardon, G., Harfe, B. D. & Tabin, C. J. A Tcf4-positive mesodermal population provides a prepattern for vertebrate limb muscle patterning. Dev. Cell 5, 937–944 (2003)

    Article  CAS  Google Scholar 

  20. Relaix, F. et al. The transcriptional activator PAX3-FKHR rescues the defects of Pax3 mutant mice but induces a myogenic gain-of-function phenotype with ligand-independent activation of Met signaling in vivo. Genes Dev. 17, 2950–2965 (2003)

    Article  CAS  Google Scholar 

  21. Mauro, A. Satellite cell of skeletal muscle fibers. J. Biophys. Biochem. Cytol. 9, 493–495 (1961)

    Article  CAS  Google Scholar 

  22. Armand, O., Boutineau, A. M., Mauger, A., Pautou, M. P. & Kieny, M. Origin of satellite cells in avian skeletal muscles. Arch. Anat. Microsc. Morphol. Exp. 72, 163–181 (1983)

    CAS  Google Scholar 

  23. Gros, J., Manceau, M., Thomé, V. & Marcelle, C. A common somitic origin for embryonic muscle progenitors and satellite cells. Nature advance online publication, 20 April 2005 (doi:10.1038/nature03572).

  24. Tajbakhsh, S., Rocancourt, D. & Buckingham, M. Muscle progenitor cells failing to respond to positional cues adopt non-myogenic fates in myf-5 null mice. Nature 384, 266–270 (1996)

    Article  ADS  CAS  Google Scholar 

  25. Ben-Yair, R. & Kalcheim, C. Lineage analysis of the avian dermomyotome sheet reveals the existence of single cells with both dermal and muscle progenitor fates. Development 132, 689–701 (2005)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank B. Williamson for critical reading of the manuscript and C. Bodin for histology work. This work was supported by the Pasteur Institute and the CNRS, with additional grants from the A.F.M., the ‘Cellules Souches’ Grand Programme Horizontal of the Pasteur Institute, the Cells into Organs Network of Excellence and the EuroStemCell Integrated Project of the EU Sixth Framework Programme.

Author information

Authors and Affiliations

  1. C.N.R.S. URA 2578, Department of Developmental Biology, Pasteur Institute, 75724, Paris, Cedex 15, France

    Frédéric Relaix, Didier Rocancourt & Margaret Buckingham

  2. Department of Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, D-37077, Gottingen, Germany

    Ahmed Mansouri

Authors
  1. Frédéric Relaix
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Didier Rocancourt
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Ahmed Mansouri
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Margaret Buckingham
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding authors

Correspondence to Frédéric Relaix or Margaret Buckingham.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure S1

A population of muscle progenitor cells that express Pax3 and Pax7, but no myogenic markers are found in the developing limb and somites. The GFP reporter targeted to Pax3 is sufficiently stable to perdure in the myogenic derivatives of these cells. (JPG 453 kb)

Supplementary Figure S1 Legend

Full legend to accompany Supplementary Figure S1. (DOC 50 kb)

Supplementary Figure S2

Demonstration of the differential stabilities of LacZ and GFP reporters targeted to Pax7 and Pax3 respectively. This is shown for the neural tube where GFP continues to be detected in cells which have moved ventrally and no longer express Pax3. (JPG 141 kb)

Supplementary Figure S2 Legend

Full legend to accompany Supplementary Figure S2. (DOC 31 kb)

Supplementary Figure S3

Transcripts for the myogenic determination factor, Myf5, are still detectable in the Pax3/Pax7 double mutant. This indicates that the early myotome is formed in the absence of these Pax factors, which are essential for subsequent skeletal muscle formation. (JPG 151 kb)

Supplementary Figure Legend S3

Full legend to accompany Supplementary Figure S3. (DOC 23 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Relaix, F., Rocancourt, D., Mansouri, A. et al. A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. Nature 435, 948–953 (2005). https://doi.org/10.1038/nature03594

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature03594

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing