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

Abstract

During vertebrate development, successive phases of embryonic and fetal myogenesis lead to the formation and growth of skeletal muscles. Although the origin and molecular regulation of the earliest embryonic muscle cells is well understood, 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.

The homeobox gene Arx is a novel positive regulator of embryonic myogenesis

“…The mutant and transgenic animals and genotyping primers used in this work were published: Pax3 GFP , 5 Arx nlacZ , 13 Tg: 3F-nlacZ-2E, 37 MyoD À/À , 38 Myf5 GFPÀP , Myf5 loxP , Myf5 nlacZ . 7,39 In Tg:3F-nlacZ-2E mice, b-galactosidase expression is restricted to differentiated skeletal and cardiac muscle.…”

“…3 Embryonic, fetal myoblasts and satellite cells derive from a Pax3/Pax7-positive population of myogenic progenitors resident in the dermomyotome. 4,5 During skeletal muscle development these mesoderm-derived progenitors generate myoblasts, which become postmitotic and then terminally differentiate into multinucleated myotubes. The muscle regulatory factors (MRFs) MyoD, Myf5, Mrf4 and Myogenin 6 are key regulators of the myogenic program and when transfected in fibroblasts, can convert them to a myogenic fate.…”

Pax3 activation promotes the differentiation of mesenchymal stem cells toward the myogenic lineage

“…Recently, galectin-1 has been identified as a soluble factor present in myoblast-conditioned medium, that has the capacity to promote myogenic conversion of dermal fibroblasts [17] and fetal MSCs [15]. This conversion seems to occur via activation of the myogenic regulatory factors (MRFs), including Myf-5, MyoD, and myogenin [15], as observed during embryonic myogenesis [18][19][20]. Another reported approach [21] made use of activated Notch to generate skeletal muscle cells from human MSCs.…”

Synergistic effects of TGFβ2, WNT9a, and FGFR4 signals attenuate satellite cell differentiation during skeletal muscle development

“…At the embryonic stage, PAX7 is first expressed in the central dermomyotome and then colocalized with PAX3 in the myotome (Relaix, Rocancourt, Mansouri & Buckingham, 2005). The PAX3 + /PAX7 + cells then become embryonic muscle progenitor cells, which enter into the myogenic process and are differentiated into myoblasts with the expression of MYF5 and MYOD (Bober et al., 1991; Rudnicki et al., 1993; Sassoon et al., 1989).…”