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

Olguín, Hugo C.; Yang, Zhihong; Tapscott, Stephen J.; Olwin, Bradley B.

doi:10.1083/jcb.200608122

Cited by 263 publications

(311 citation statements)

References 38 publications

(90 reference statements)

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“…Rage -/-myoblasts have higher levels of Pax7, greater proliferation potential and lower differentiation potential than WT myoblasts, and deleting Rage promotes asymmetric division of myoblasts 42 . MyoD and MyoG downregulate Pax7 post-translationally 43 ; however, in myoblasts committed to differentiation, post-transcriptional downregulation is mediated by miR-1, miR-206 and miR-486 (refs 30,44). Here we showed that miR-431 regulates SC functions in miR-431 TG mice and we provide convincing evidence that the Pax7 level is tightly controlled by miR-431 in SCs in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice

Zhai

et al. 2015

Nat Commun

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Skeletal muscle stem cells, called satellite cells, are a quiescent heterogeneous population. Their heterogeneity is influenced by Pax7, a well-defined transcriptional regulator of satellite cell functions that defines two subpopulations: Pax7 Hi and Pax7 Lo . However, the mechanisms by which these subpopulations are established and maintained during myogenesis are not completely understood. Here we show that miR-431, which is predominantly expressed in the skeletal muscle, mediates satellite cell heterogeneity by fine-tuning Pax7 levels during muscle development and regeneration. In miR-431 transgenic mice, the Pax7 Lo subpopulation is enriched, enhances myogenic differentiation and accelerates muscle regeneration. Notably, miR-431 attenuates the muscular dystrophic phenotype in mdx mice and may be a potential therapeutic target in muscular diseases. miR-431 transgenic mice are a unique genetic model for investigating the cellular features and biological functions of Pax7 Lo satellite cells during muscle development and regeneration.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice

Zhai

et al. 2015

Nat Commun

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“…Thus, by inducing the expression of Id2 and Id3, Pax7 may act to block the premature differentiation of quiescent satellite cells. In addition, Pax7 may also block skeletal muscle differentiation by targeting myogenic bHLH proteins for degradation (Olguin et al, 2007). In contrast, in activated satellite cells, Pax7 may act to directly induce the expression of Myf5 (Bajard et al, 2006) and MyoD (Hu et al, 2008), which in turn will compete with Id proteins for E protein dimerization.…”

Section: Discussionmentioning

confidence: 99%

Id3 Is a Direct Transcriptional Target of Pax7 in Quiescent Satellite Cells

Kumar

Shadrach

Wagers

et al. 2009

MBoC

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INTRODUCTIONPax3 and Pax7 are two closely related transcription factors that are expressed in the dermomyotome, and they have been shown to be essential for generation of all fetal trunk musculature . Pax3/7-expressing dermomyotomal cells have recently been shown to give rise to skeletal muscle progenitors, termed satellite cells, in the adult (Gros et al., 2005;Kassar-Duchossoy et al., 2005;Relaix et al., 2005;Schienda et al., 2006). Satellite cells are a small population of myogenic progenitors that reside between the sarcolemma and basal lamina of the muscle fiber, and they play a crucial role in postnatal muscle growth and regeneration (reviewed in Zammit et al., 2006). Following skeletal muscle injury or exercise-induced activation, the normally quiescent Pax7-expressing satellite cells proliferate extensively and up-regulate expression of MyoD (Smith et al., 2001;Yan et al., 2003;Montarras et al., 2005) and Myf-5 (Conboy and Rando, 2002;Yan et al., 2003), before differentiation into skeletal muscle.Pax3 and Pax7 are members of the Pax transcription factor family and contain both paired (PD) and homeodomain (HD) DNA binding motifs. Pax3 and Pax7 can bind to DNA sequences containing either a consensus paired domain binding site (GTCAC A/G C/G A/T T/C) or a homeodomain binding site (ATTA) (Chalepakis et al., 1994;Chalepakis and Gruss, 1995). Pax3 and Pax7 activate MyoD expression (Maroto et al., 1997;Tajbakhsh et al., 1997;Relaix et al., 2003Relaix et al., , 2004, and recently Pax3 has been shown to directly bind sequences that regulate the expression of either MyoD in C2C12 cells (Hu et al., 2008) or Myf-5 during development of hypaxial muscle (Bajard et al., 2006). Although it is clear that Pax3/7 can directly induce the expression of Myf5 (Bajard et al., 2006), MyoD (Hu et al., 2008), and fibroblast growth factor receptor 4 (Lagha et al., 2008), other relevant targets for Pax3/7 in satellite cells have yet to be identified. To identify potential targets for Pax3/7 in satellite cells, we examined the transcriptional profile of genes induced by these transcription factors in the C2C12 muscle cell line. Of the genes identified, we found that a subset were also expressed in quiescent satellite cells and therefore they could potentially be direct targets of Pax7 in these cells. In this report, we focus on two such putative Pax3/7 transcriptional targets, inhibitor of DNA binding (Id) 2 and Id3, which we found to be expressed in quiescent satellite cells. We report that Pax3/7 can drive expression of both Id2 and Id3 in C2C12 cells under low serum conditions, that the Id3 promoter contains a conserved Pax3/7 binding site, and that Pax3/7 can activate expression of a reporter construct driven by the Id3 promoter. In addition, we demonstrate that Pax7 is normally bound to the Id3 promoter in quiescent satellite cells and that short hairpin RNA (shRNA)-mediated knockdown of Pax7 expression in cultured satellite cells Abbreviations used: C1R, complement component 1 R subunit; ChIP, chromatin immunoprecipitation; CS...

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“…There are four main MRFs that control normal myogenesis: Myf5, MyoD, MRF4, and myogenin. The paired box transcription factor Pax7 is a key protein that coordinates the transcription of the MRFs and progression of SCs through the developmental pathway known as the myogenic program (8,16,39,43,44). SCs have been implicated as a significant factor contributing to the inability of aged muscle to repair/ remodel.…”

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confidence: 99%

Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction

McKay

Ogborn

Baker

et al. 2013

American Journal of Physiology-Cell Physiology

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

Cited by 263 publications

References 38 publications

MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice

MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice

Id3 Is a Direct Transcriptional Target of Pax7 in Quiescent Satellite Cells

Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction

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