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 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.
Olguin
Hugo C
HC
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Yang
Zhihong
Z
Tapscott
Stephen J
SJ
Olwin
Bradley B
BB
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D051379:Mice; D024510:Muscle Development / Q000502:physiology; D017570:MyoD Protein / Q000037:antagonists & inhibitors / Q000502:physiology*; D018008:Myogenin / Q000502:physiology; D051763:PAX7 Transcription Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018008:Myogenin; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse