Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors

Young, Arthur P.; Wagers, Amy J.

doi:10.1242/jcs.061606

Cited by 34 publications

(20 citation statements)

References 47 publications

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“…In avian muscle, MPCs located in muscle spindles also express Pax3 and may be involved in maintaining myofibers (Kirkpatrick et al 2010). Pax3 may also play a role in inducing differentiation (Young and Wagers 2010), a finding supported by positive Pax3 staining in differentiating giant danio myoblasts. Interestingly, in the immortalized C2C12 myogenic cell line commonly used in investigations of myogenesis, Pax3 attenuates differentiation, while ectopic expression induces differentiation in primary murine myoblasts (Young and Wagers 2010).…”

Section: Discussionmentioning

confidence: 92%

In vitro indeterminate teleost myogenesis appears to be dependent on Pax3

Froehlich

Galt

Charging

et al. 2013

In Vitro Cell.Dev.Biol.-Animal

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The zebrafish (Danio rerio) has been used extensively as a model system for developmental studies but, unlike most teleost fish, it grows in a determinate-like manner. A close relative, the giant danio (Devario cf. aequipinnatus), grows indeterminately, displaying both hyperplasia and hypertrophy of skeletal myofibers as an adult. To better understand adult muscle hyperplasia, a postlarval/postnatal process that closely resembles secondary myogenesis during development, we characterized the expression of Pax3/7, c-Met, syndecan-4, Myf5, MyoD1, myogenin, and myostatin during in vitro myogenesis, a technique that allows for the complete progression of myogenic precursor cells to myotubes. Pax7 appears to be expressed only in newly activated MPCs while Pax3 is expressed through most of the myogenic program, as are c-Met and syndecan-4. MyoD1 appears important in all stages of myogenesis, while Myf5 is likely expressed at low to background levels, and myogenin expression is enriched in myotubes. Myostatin, like MyoD1, appears to be ubiquitous at all stages. This is the first comprehensive report of key myogenic factor expression patterns in an indeterminate teleost, one that strongly suggests that Pax3 and/or Myf5 may be involved in the regulation of this paradigm. Further, it validates this species as a model organism for studying adult myogenesis in vitro, especially mechanisms underlying nascent myofiber recruitment.

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Section: Discussionmentioning

confidence: 92%

In vitro indeterminate teleost myogenesis appears to be dependent on Pax3

Froehlich

Galt

Charging

et al. 2013

In Vitro Cell.Dev.Biol.-Animal

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“…Skeletal muscle progenitor stem cells express cell context-specific genes involved in tissue regeneration (37). Embryonic skeletal muscle requires paired-box transcriptional factors (Pax3 and Pax7) and canonical myogenic regulatory factors (MRFs; Myf-5, MyoD, myogenin and Mrf4) for its development (38). During regeneration of skeletal muscle, Pax7 and MyoD expressed in quiescent and activated satellite stem cells specifically determines and regulates cell lineage during skeletal muscle regeneration (39-42).…”

Section: Introductionmentioning

confidence: 99%

Nrf2 deficiency promotes apoptosis and impairs PAX7/MyoD expression in aging skeletal muscle cells

Narasimhan

Hong

Atieno

et al. 2014

Free Radical Biology and Medicine

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Skeletal muscle redox homoeostasis is transcriptionally regulated by nuclear erythroid-2-p45-related factor-2 (Nrf2). We recently demonstrated that age-associated stress impairs Nrf2-ARE (antioxidant response element) transcriptional signaling. Here, we hypothesize that age-dependent decline or genetic ablation of Nrf2 leads to accelerated apoptosis and skeletal muscle degeneration. Under basal-physiological conditions, disruption of Nrf2 significantly down regulates antioxidants and causes oxidative stress. Surprisingly, Nrf2-null mice had enhanced antioxidant capacity identical to wild-type (WT) upon acute endurance exercise stress (AEES), suggesting activation of Nrf2-independent mechanisms (i.e. PGC1α) against oxidative stress. Analysis of pro-survival pathways under the basal state reveals decreased Akt levels, while pp53, a repressor of Akt, was increased in Nrf2-null versus WT mice. Upon AEES, Akt and p-Akt levels were significantly (p<0.001) increased (>10 fold) along with profound down regulation of pp53 (p<0.01) in Nrf2-null versus WT skeletal muscle, indicating the onset of pro-survival mechanisms to compensate the loss of Nrf2 signaling. However, we found a decreased stem cell population (Pax7) and MyoD expression (differentiation) along with profound activation of ubiquitin and apoptotic pathways in Nrf2- null versus WT mice upon AEES, suggesting that compensatory pro-survival mechanisms failed to overcome the programed cell death and degeneration in skeletal muscle. Further, the impaired regeneration was sustained in Nrf2-null vs. WT mice after 1 week of post-AEES recovery. In an age-associated oxidative stress condition, ablation of Nrf2 results in induction of apoptosis and impaired muscle regeneration.

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“…5A), but no change in satellite marker Myf5 (Relaix et al . 2006, Young & Wagers 2010, Filareto et al . 2015).…”

Section: Resultsmentioning

confidence: 99%

“…It is possible that although the increased expression of MyoD1 and Pax3 may drive the proliferation and differentiation of progenitor cells (Relaix et al . 2006, Young & Wagers 2010, Filareto et al . 2015), increased expression of Ifnγ may inhibit myogenin activity and prevent differentiation (Londhe & Davie 2011).…”

Section: Resultsmentioning

confidence: 99%

Muscle injury, impaired muscle function and insulin resistance in Chromogranin A-knockout mice

Tang

Pasqua

Biswas

et al. 2017

Journal of Endocrinology

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Chromogranin A (CgA) is widely expressed in endocrine and neuroendocrine tissues as well as in the central nervous system. We observed CgA expression (mRNA and protein) in the gastrocnemius (GAS) muscle and found that performance of CgA-deficient Chga-KO mice in treadmill exercise was impaired. Supplementation with CgA in Chga-KO mice restored exercise ability suggesting a novel role for endogenous CgA in skeletal muscle function. Chga-KO mice display (i) lack of exercise-induced stimulation of pAKT, pTBC1D1 and phospho-p38 kinase signaling, (ii) loss of GAS muscle mass, (iii) extensive formation of tubular aggregates (TA), (iv) disorganized cristae architecture in mitochondria, (v) increased expression of the inflammatory cytokines Tnfα, Il6 and Ifnγ, and fibrosis. The impaired maximum running speed and endurance in the treadmill exercise in Chga-KO mice correlated with decreased glucose uptake and glycolysis, defects in glucose oxidation and decreased mitochondrial cytochrome C oxidase activity. The lack of adaptation to endurance training correlated with the lack of stimulation of p38MAPK that is known to mediate the response to tissue damage. As CgA sorts proteins to the regulated secretory pathway, we speculate that lack of CgA could cause misfolding of membrane proteins inducing aggregation of sarcoplasmic reticulum (SR) membranes and formation of tubular aggregates that is observed in Chga-KO mice. In conclusion, CgA deficiency renders the muscle energy deficient, impairs performance in treadmill exercise and prevents regeneration after exercise-induced tissue damage.

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Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors

Cited by 34 publications

References 47 publications

In vitro indeterminate teleost myogenesis appears to be dependent on Pax3

In vitro indeterminate teleost myogenesis appears to be dependent on Pax3

Nrf2 deficiency promotes apoptosis and impairs PAX7/MyoD expression in aging skeletal muscle cells

Muscle injury, impaired muscle function and insulin resistance in Chromogranin A-knockout mice

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