Integrated Functions of Pax3 and Pax7 in the Regulation of Proliferation, Cell Size and Myogenic Differentiation

Collins, Charlotte; Gnocchi, Viola F.; White, Rachel E.; Boldrin, Luisa; Ruiz, Ana Pérez; Relaix, Frédéric; Morgan, Jennifer E.; Zammit, Peter S.

doi:10.1371/journal.pone.0004475

Cited by 109 publications

(111 citation statements)

References 45 publications

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“…They function to activate and maintain expression of MRFs and promote cell expansion (16,49). Moreover, associated to their myogenic promoting activity, ectopic Pax3 or Pax7 expression restricts myoblast accretion and myotube growth (16).…”

Section: Discussionmentioning

confidence: 99%

Wnt4 activates the canonical β-catenin pathway and regulates negatively myostatin: functional implication in myogenesis

Bernardi

Gay

Fédon

et al. 2011

American Journal of Physiology-Cell Physiology

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Expression of Wnt proteins is known to be important for developmental processes such as embryonic pattern formation and determination of cell fate. Previous studies have shown that Wn4 was involved in the myogenic fate of somites, in the myogenic proliferation, and differentiation of skeletal muscle. However, the function of this factor in adult muscle homeostasis remains not well understood. Here, we focus on the roles of Wnt4 during C2C12 myoblasts and satellite cells differentiation. We analyzed its myogenic activity, its mechanism of action, and its interaction with the anti-myogenic factor myostatin during differentiation. Established expression profiles indicate clearly that both types of cells express a few Wnts, and among these, only Wnt4 was not or barely detected during proliferation and was strongly induced during differentiation. As attested by myogenic factors expression pattern analysis and fusion index determination, overexpression of Wnt4 protein caused a strong increase in satellite cells and C2C12 myoblast differentiation leading to hypertrophic myotubes. By contrast, exposure of satellite and C2C12 cells to small interfering RNA against Wnt4 strongly diminished this process, confirming the myogenic activity of Wnt4. Moreover, we reported that Wnt4, which is usually described as a noncanonical Wnt, activates the canonical ␤-catenin pathway during myogenic differentiation in both cell types and that this factor regulates negatively the expression of myostatin and the regulating pathways associated with myostatin. Interestingly, we found that recombinant myostatin was sufficient to antagonize the differentiation-promoting activities of Wnt4. Reciprocally, we also found that the genetic deletion of myostatin renders the satellite cells refractory to the hypertrophic effect of Wnt4. These results suggest that the Wnt4-induced decrease of myostatin plays a functional role during hypertrophy. We propose that Wnt4 protein may be a key factor that regulates the extent of differentiation in satellite and C2C12 cells. satellite cells; C2C12 myoblasts; muscle hypertrophy; muscle differentiation

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Section: Discussionmentioning

confidence: 99%

Wnt4 activates the canonical β-catenin pathway and regulates negatively myostatin: functional implication in myogenesis

Bernardi

Gay

Fédon

et al. 2011

American Journal of Physiology-Cell Physiology

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“…PAX7 is expressed in, and marks, quiescent and proliferating SCs and myoblasts and is repressed in differentiating myoblasts (Collins et al, 2009;Relaix et al, 2005;Relaix et al, 2006;Seale et al, 2000). The expression of PAX7 and myogenin is mutually exclusive in SCs and myoblasts: downregulation of PAX7 is required for myoblast terminal differentiation, and sustained expression of PAX7 in SCs delays the onset of myogenesis and stimulates acquisition of a quiescent state (Olguin and Olwin, 2004;Zammit et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

HMGB1/RAGE regulates muscle satellite cell homeostasis via p38 MAPK/myogenin-dependent repression of Pax7 transcription

Riuzzi

Sorci

Sagheddu

et al. 2012

Journal of Cell Science

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SummaryExpression of the paired-box 7 (PAX7) transcription factor is regulated during both myoblast proliferation and differentiation: high levels of PAX7 compromise myogenic differentiation because of excess and prolonged proliferation, whereas low levels of PAX7 result in precocious differentiation. We showed that myogenin repressed Pax7 transcription in differentiating myoblasts by binding to specific recognition sites in the Pax7 promoter, and that high-mobility group box 1 (HMGB1)-receptor for advanced glycation end-products (RAGE) signaling was required for myogenin induction and myogenin-dependent repression of Pax7 transcription. In addition, PAX7 negatively and myogenin positively regulated RAGE expression. RAGE, a multiligand receptor of the immunoglobulin superfamily, was not expressed in adult skeletal muscles, and was transiently expressed in activated, proliferating and differentiating satellite cells (SCs) in injured muscles. Compared with wild-type muscles, Rage -/-muscles exhibited increased numbers of basal SCs that were further increased in injured Rage -/-muscles following elevated myoblast asymmetric division; complete regeneration of injured Rage -/-muscles was found to be delayed by ,1 week. Thus, RAGE signaling physiologically repressed Pax7 transcription in SCs by upregulating myogenin, thereby accelerating muscle regeneration and limiting SC self-renewal.

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“…The presence of Pax7 is also necessary for production of other muscle regulatory factors -MyoD and Myf5 [23]. Moreover, Pax7 plays a crucial role in the processes of proliferation, differentiation, and selfrenewal [24]. Satellite cells also produce the paralog of Pax7 -Pax3 which was detected at a relatively high level only in some muscle types, e.g.…”

Section: Satellite Cellsmentioning

confidence: 99%

Adult stem cells derived from skeletal muscle — biology and potential

2013

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Skeletal muscle contains at least two distinct populations of adult stem cells — satellite cells and multipotent muscle-derived stem cells. Monopotential satellite cells are located under the basal lamina of muscle fibers. They are capable of giving rise only to cells of myogenic lineage, which play an important role in the processes of muscle regeneration. Multipotent muscle-derived stem cells are considered to be predecessors of the satellite cells. Under proper conditions, both in vitro and in vivo, they undergo myogenic, cardiogenic, chondrogenic, osteogenic and adipogenic differentiation. The main purpose of the present article is to summarize current information about adult stem cells derived from skeletal muscle, and to discuss their isolation and in vitro expansion techniques, biological properties, as well as their potential for regenerative medicine.

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Integrated Functions of Pax3 and Pax7 in the Regulation of Proliferation, Cell Size and Myogenic Differentiation

Cited by 109 publications

References 45 publications

Wnt4 activates the canonical β-catenin pathway and regulates negatively myostatin: functional implication in myogenesis

Wnt4 activates the canonical β-catenin pathway and regulates negatively myostatin: functional implication in myogenesis

HMGB1/RAGE regulates muscle satellite cell homeostasis via p38 MAPK/myogenin-dependent repression of Pax7 transcription

Adult stem cells derived from skeletal muscle — biology and potential

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