Title: A Pax3/Pax7-dependent population of skeletal muscle progenitor cells
Abstract: A new population of stem cells, present in skeletal muscle, has been identified in two independent studies. The cells are important in the formation of skeletal muscle in the embryo and fetus. The origin of early embryonic muscle cells is well understood, but less is known about the later stages, where progenitor cells in the muscle mass continuously form new cells in the fetus. Relaix et al. identify cells in mice that continue to proliferate in the trunk and limbs during development. These cells express the transcription factors Pax3 and Pax7, the absence of which causes later muscle development to fail. Gros et al. trace lineage in the chick to show that the origin of this cell population is in a region of the embryo called the somite, and that these cells give rise to satellite cells — the committed stem cells of adult skeletal muscle. Greater understanding of the origin of muscle cells may help in developing therapies to combat muscle disease. 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.