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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.

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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.

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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.

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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
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  2. Didier Rocancourt
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  3. Ahmed Mansouri
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  4. Margaret Buckingham
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Corresponding authors

Correspondence to Frédéric Relaix or Margaret Buckingham.

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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)

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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

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