Pax7 is critical for the normal function of satellite cells in adult skeletal muscle
Open Access
- 24 September 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 110 (41), 16474-16479
- https://doi.org/10.1073/pnas.1307680110
Abstract
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.Keywords
This publication has 24 references indexed in Scilit:
- The emerging biology of muscle stem cells: Implications for cell‐based therapiesBioEssays, 2012
- Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in MuscleCell, 2007
- Distinct roles for Pax7 and Pax3 in adult regenerative myogenesisThe Journal of cell biology, 2006
- Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cellsThe Journal of cell biology, 2005
- Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewalDevelopmental Biology, 2004
- Muscle satellite cell-specific genes identified by genetic profiling of MyoD-deficient myogenic cellDevelopmental Biology, 2004
- Rb is required for progression through myogenic differentiation but not maintenance of terminal differentiationThe Journal of cell biology, 2004
- Pax7 directs postnatal renewal and propagation of myogenic satellite cells but not their specificationThe EMBO Journal, 2004
- Pax7 Is Necessary and Sufficient for the Myogenic Specification of CD45+:Sca1+ Stem Cells from Injured MusclePLoS Biology, 2004
- Pax7 Is Required for the Specification of Myogenic Satellite CellsCell, 2000