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Pax-7 up-regulation inhibits myogenesis ... tial mechanism for self-renewal


Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewal.

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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 HC, Olwin BB

Developmental biology

2004-11-15 00:00

275

2

375-88

Animals,Blotting, Western,Cell Cycle,Cell Line,Fluorescent Antibody Technique,Gene Expression Regulation,Homeodomain Proteins,Mice,Mice, Mutant Strains,Models, Biological,Muscle Development,Myoblasts,PAX7 Transcription Factor,Satellite Cells, Skeletal Muscle,Transfection,Homeodomain Proteins,PAX7 Transcription Factor,Pax7 protein, mouse

Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA

Dev. Biol.

NIAMS AR39467

0012-1606

10.1016/j.ydbio.2004.08.015

S0012-1606(04)00552-4

883

True

15501225

Hugo Olguin
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