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

Olguín, Hugo C.; Olwin, Bradley B.

doi:10.1016/j.ydbio.2004.08.015

Cited by 480 publications

(514 citation statements)

References 25 publications

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“…miR-431 promotes myogenic differentiation by targeting Pax7. Decreased Pax7 expression is required to initiate myogenic differentiation 21 . In C2C12 cells, as in SCs (Fig.…”

Section: Resultsmentioning

confidence: 99%

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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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“…miR-431 promotes myogenic differentiation by targeting Pax7. Decreased Pax7 expression is required to initiate myogenic differentiation 21 . In C2C12 cells, as in SCs (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Pax7 is expressed abundantly in quiescent SCs but at much lower levels in activated SCs. Furthermore, Pax7 downregulation is required for myogenic differentiation 21 . However, the mechanism that governs Pax7 expression in SCs during muscle development and regeneration is unclear.…”

mentioning

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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“…In Smad3-null mice, there is a significant reduction in the SC number ( Figure 2E and 2F), and data presented here suggest that this could be due to reduced self-renewal of SCs ( Figure 2B and 2D). SC self-renewal refers to a process whereby a pool of myoblasts (derived from activated SCs), which express high levels of Pax7, withdraws from proliferation to replenish the SC population [28,29]. Therefore, proliferation rate plays an important role in determining the pool of self-renewed SCs [8] during postnatal myogenesis.…”

Section: Smad3 Signaling Is Required For Proper Function Of Scsmentioning

confidence: 99%

Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts

McFarlane

Vajjala

et al. 2011

Cell Res

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TGF-β and myostatin are the two most important regulators of muscle growth. Both growth factors have been shown to signal through a Smad3-dependent pathway. However to date, the role of Smad3 in muscle growth and differentiation is not investigated. Here, we demonstrate that Smad3-null mice have decreased muscle mass and pronounced skeletal muscle atrophy. Consistent with this, we also find increased protein ubiquitination and elevated levels of the ubiquitin E3 ligase MuRF1 in muscle tissue isolated from Smad3-null mice. Loss of Smad3 also led to defective satellite cell (SC) functionality. Smad3-null SCs showed reduced propensity for self-renewal, which may lead to a progressive loss of SC number. Indeed, decreased SC number was observed in skeletal muscle from Smad3-null mice showing signs of severe muscle wasting. Further in vitro analysis of primary myoblast cultures identified that Smad3-null myoblasts exhibit impaired proliferation, differentiation and fusion, resulting in the formation of atrophied myotubes. A search for the molecular mechanism revealed that loss of Smad3 results in increased myostatin expression in Smad3-null muscle and myoblasts. Given that myostatin is a negative regulator, we hypothesize that increased myostatin levels are responsible for the atrophic phenotype in Smad3-null mice. Consistent with this theory, inactivation of myostatin in Smad3-null mice rescues the muscle atrophy phenotype.

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“…In Pax7 mutants, satellite muscle cells are formed, but in reduced numbers that fall further over time (Zammit et al, 2004). In addition, forced expression of Pax7 in satellite cells prevents their difference into myoblasts (Olguin and Olwin, 2004). Similarly the activity of Pax6 is involved in conferring progenitor status to neuronal populations in the spinal cord, cerebral cortex, adult hippocampus, and olfactory bulb (Grindley et al, 1995;Kohwi et al, 2005;Bel-Vialar et al, 2007;Tucker et al, 2008).…”

Section: Control Of Cell Division By Pax2mentioning

confidence: 99%

Pax2 modulates proliferation during specification of the otic and epibranchial placodes

Freter¹,

Muta²,

O’Neill³

et al. 2012

Developmental Dynamics

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Background: The inner ear and epibranchial ganglia of vertebrates arise from a shared progenitor domain that is induced by FGF signalling, the posterior placodal area (PPA), before being segregated by Wnt signalling. One of the first genes activated in the PPA is the transcription factor Pax2. Loss-of-and gain-of function studies have defined a role for Pax2 in placodal morphogenesis and later inner ear development, but have not addressed the role Pax2 plays during the formation and maintenance of the PPA. Results: To understand the role of Pax2 during the development of the PPA, we used over-expression and repression of Pax2. Both gave rise to a smaller otocyst and repressed the formation of epibranchial placodes. In addition, cell cycle analysis revealed that Pax2 suppression reduced proliferation of the PPA. Key FindingsNeither suppression nor over-expression of Pax2 affects the extent of the precursor region of the inner ear and epibranchial placodes, the PPA. Suppressing and over-expressing Pax2 does affect the differentiation of the inner ear and the epibranchial placodes. Pax2 suppression reduces proliferation of PPA precursors.

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

Cited by 480 publications

References 25 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

Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts

Pax2 modulates proliferation during specification of the otic and epibranchial placodes

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