Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewal.
Satellite cells are myogenic precursors responsible for skeletal muscle regeneration. Satellite cells are absent in the Pax-7-/- mouse, suggesting that this transcription factor is crucial for satellite cell specification [Seale, P., Sabourin, L.A., Girgis-Gabardo, A., Mansouri, A., Gruss, P., Rudnicki, M.A., 2000. Pax7 is required for the specification of myogenic satellite cells. Cell 102, 777-786]. Analysis of Pax-7 expression in activated satellite cells unexpectedly revealed substantial heterogeneity within individual clones. Further analyses show that Pax-7 and myogenin expression are mutually exclusive during differentiation, where Pax-7 appears to be up-regulated in cells that escape differentiation and exit the cell cycle, suggesting a regulatory relationship between these two transcription factors. Indeed, overexpression of Pax-7 down-regulates MyoD, prevents myogenin induction, and blocks MyoD-induced myogenic conversion of 10T1/2 cells. Overexpression of Pax-7 also promotes cell cycle exit even in proliferation conditions. Together, these results suggest that Pax-7 may play a crucial role in allowing activated satellite cells to reacquire a quiescent, undifferentiated state. These data support the concept that satellite cell self-renewal may be a primary mechanism for replenishment of the satellite cell compartment during skeletal muscle regeneration.
Olguin
Hugo C
HC
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Olwin
Bradley B
BB
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D024510:Muscle Development / Q000502:physiology*; D032446:Myoblasts; D051763:PAX7 Transcription Factor; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*; D014162:Transfection
D018398:Homeodomain Proteins; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse