Pax7 is critical for the normal function of satellite cells in adult skeletal muscle.
Extensive analyses of mice carrying null mutations in paired box 7 (Pax7) have confirmed the progressive loss of the satellite cell lineage in skeletal muscle, resulting in severe muscle atrophy and death. A recent study using floxed alleles and tamoxifen-induced inactivation concluded that after 3 wk of age, Pax7 was entirely dispensable for satellite cell function. Here, we demonstrate that Pax7 is an absolute requirement for satellite cell function in adult skeletal muscle. Following Pax7 deletion, satellite cells and myoblasts exhibit cell-cycle arrest and dysregulation of myogenic regulatory factors. Maintenance of Pax7 deletion through continuous tamoxifen administration prevented regrowth of Pax7-expressing satellite cells and a profound muscle regeneration deficit that resembles the phenotype of skeletal muscle following genetically engineered ablation of satellite cells. Therefore, we conclude that Pax7 is essential for regulating the expansion and differentiation of satellite cells during both neonatal and adult myogenesis.
Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H 8L6.
Julia
J
von Maltzahn
Andrew E
AE
Jones
Robin J
RJ
Parks
Michael A
MA
Rudnicki
D000818:Animals; D015153:Blotting, Western; D005260:Female; D005455:Fluorescent Antibody Technique; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D051763:PAX7 Transcription Factor / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000502:physiology*; D013629:Tamoxifen
D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D013629:Tamoxifen
CreERT2; stem cell