Reciprocal inhibition between Pax7 and muscle regulatory factors modulates myogenic cell fate determination

Postnatal growth and regeneration of skeletal muscle requires a population of resident myogenic precursors named satellite cells. The transcription factor Pax7 is critical for satellite cell biogenesis and survival and has been also implicated in satellite cell self-renewal; however, the underlying...

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Published inThe Journal of cell biology Vol. 177; no. 5; pp. 769 - 779
Main Authors Olguin, Hugo C, Yang, Zhihong, Tapscott, Stephen J, Olwin, Bradley B
Format Journal Article
LanguageEnglish
Published United States The Rockefeller University Press 04.06.2007
Rockefeller University Press
Subjects
Animals
Artificial satellites
Cell Differentiation - physiology
Cell growth
Cell Line
Cell lines
Cell Proliferation
Cells
Cellular differentiation
DNA
Down regulation
Gene Expression Regulation
Mice
Molecular biology
Muscle development
Muscle Development - physiology
Musculoskeletal system
Myoblasts
MyoD Protein - antagonists & inhibitors
MyoD Protein - physiology
Myogenin - physiology
PAX7 Transcription Factor - antagonists & inhibitors
PAX7 Transcription Factor - chemistry
PAX7 Transcription Factor - physiology
Protein Interaction Mapping
Protein Structure, Tertiary
Proteins
Reporter genes
Satellite Cells, Skeletal Muscle - cytology
Skeletal muscle satellite cells
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Summary:Postnatal growth and regeneration of skeletal muscle requires a population of resident myogenic precursors named satellite cells. The transcription factor Pax7 is critical for satellite cell biogenesis and survival and has been also implicated in satellite cell self-renewal; however, the underlying molecular mechanisms remain unclear. Previously, we showed that Pax7 overexpression in adult primary myoblasts down-regulates MyoD and prevents myogenin induction, inhibiting myogenesis. We show that Pax7 prevents muscle differentiation independently of its transcriptional activity, affecting MyoD function. Conversely, myogenin directly affects Pax7 expression and may be critical for Pax7 down-regulation in differentiating cells. Our results provide evidence for a cross-inhibitory interaction between Pax7 and members of the muscle regulatory factor family. This could represent an additional mechanism for the control of satellite cell fate decisions resulting in proliferation, differentiation, and self-renewal, necessary for skeletal muscle maintenance and repair.
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Correspondence to Bradley B. Olwin: Bradley.Olwin@colorado.edu
Abbreviations used in this paper: EMSA, electrophoretic mobility shift assay; MRF, muscle regulatory factor; MyHC, myosin heavy chain.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200608122