Myf5 mRNA Levels Research Articles

Dietary vitamin E further enhances the effectiveness of Clostridium autoethanogenum protein as an alternative source of soybean meal in grass carp (Ctenopharygodon idellus) diets based on growth performance, flesh quality and antioxidant status

The effects of replacing soybean meal with Clostridium autoethanogenum protein and supplementing it with different gradients of vitamin E in grass carp diets on growth performance, flesh quality and antioxidant capacity were evaluated in a 69-day feeding trial. Five isonitrogen and isolipid diets were configured with the soybean meal-based diet (SM) served as the basal control diet, and the Clostridium autoethanogenum protein-based diet (CAP) as the treatment control diet. The CAP diet was supplemented with 80 mg/kg, 160 mg/kg and 240 mg/kg vitamin E (namely, 80VE, 160VE and 240VE), respectively. Final body weight (FBW) and specific growth rate (SGR) were significantly better in the CAP group than in the SM group (P < 0.05), and the 160 VE group was significantly better than the CAP group (P < 0.05). In terms of muscle quality, muscle fat content was significantly higher in the CAP group than in the SM group (P < 0.05), and muscle vitamin E content was significantly higher in each vitamin E-supplemented group than in the CAP group (P > 0.05). The total odor activity value in muscle in the CAP group was not significantly different from the SM group (P < 0.05), but the vitamin E-supplemented groups were significantly higher than the CAP group (P < 0.05). Muscle hardness and gumminess were significantly higher in the CAP group than the SM group and muscle shear force and gumminess were significantly higher in the 80VE group than the CAP group (P < 0.05). Muscle development-related genes in the CAP group were not significantly different from those in the SM group (P > 0.05), and Muscle Myf5 mRNA levels in the 160VE and 240VE groups were significantly higher than those in the CAP group, while the expression of MSTN genes was suppressed (P < 0.05). In terms of antioxidant properties, muscle MDA content was significantly higher in the CAP group than in the SM group (P < 0.05), and muscle MDA content was significantly lower in the 160VE and 240VE groups than in the CAP group (P < 0.05), at the same time, CAT and T-SOD activities were significantly higher (P < 0.05). In conclusion, complete replacement of soybean meal by the Clostridium autoethanogenum protein in grass carp diets promoted growth performance and muscle quality, but negatively affected antioxidant capacity, and supplementation of 160 mg/kg vitamin E in the CAP diet could further enhance growth performance and improve antioxidant capacity.

Higher strength gain after hypoxic vs normoxic resistance training despite no changes in muscle thickness and fractional protein synthetic rate.

Acute hypoxia has previously been suggested to potentiate resistance training-induced hypertrophy by activating satellite cell-dependent myogenesis rather than an improvement in protein balance in human. Here, we tested this hypothesis after a 4-week hypoxic vs normoxic resistance training protocol. For that purpose, 19 physically active male subjects were recruited to perform 6 sets of 10 repetitions of a one-leg knee extension exercise at 80% 1-RM 3 times/week for 4weeks in normoxia (FiO2 : 0.21; n=9) or in hypoxia (FiO2 : 0.135, n=10). Blood and skeletal muscle samples were taken before and after the training period. Muscle fractional protein synthetic rate was measured over the whole period by deuterium incorporation into the protein pool and muscle thickness by ultrasound. At the end of the training protocol, the strength gain was higher in the hypoxic vs the normoxic group despite no changes in muscle thickness and in the fractional protein synthetic rate. Only early myogenesis, as assessed by higher MyoD and Myf5 mRNA levels, appeared to be enhanced by hypoxia compared to normoxia. No effects were found on myosin heavy chain expression, markers of oxidative metabolism and lactate transport in the skeletal muscle. Though the present study failed to unravel clearly the mechanisms by which hypoxic resistance training is particularly potent to increase muscle strength, it is important message to keep in mind that this training strategy could be effective for all athletes looking at developing and optimizing their maximal muscle strength.

The Effect of Continuous Light on Growth and Muscle-Specific Gene Expression in Atlantic Salmon (Salmo salar L.) Yearlings.

Photoperiod is associated to phenotypic plasticity of somatic growth in several teleost species, however, the molecular mechanisms underlying this phenomenon are currently unknown. The effect of a continuous lighting (LD 24:0), compared with the usual hatchery lighting (HL) regime, on the growth rate and gene expression of myogenic regulatory factors (MRFs: MyoD1 paralogs, Myf5, and MyoG) myosin heavy chain (MyHC), and MSTN paralogs in the white muscles of hatchery-reared Atlantic salmon yearlings was evaluated over a 6-month period (May–October). The levels of gene expression were determined using real-time PCR. Continuous lighting was shown to have a positive effect on weight gain. MyHC, MyoD1c, MyoD1b, and MSTN1a/b mRNA expression was influenced by the light regime applied. In all the studied groups, a significant positive correlation was observed between the expression levels of MRFs and MSTN paralogs throughout the experiment. The study demonstrated seasonal patterns regarding the simultaneous expression of several MRFs. MyoD1a, MyoG, and MyHC mRNA expression levels were elevated in the mid-October, but MyoD1b/c, and Myf5 mRNA levels decreased by the end of this month. In general, the findings showed that constant lighting affected the regulatory mechanisms of muscle growth processes in salmon.

Mild hyperbaric oxygen inhibits the growth-related decline in skeletal muscle oxidative capacity and prevents hyperglycemia in rats with type 2 diabetes mellitus.

Humans and animals with type 2 diabetes mellitus (T2DM) exhibit low skeletal muscle oxidative capacity and impaired glucose metabolism. The aim of the present study was to investigate the effects of exposure to mild hyperbaric oxygen on these changes in obese rats with T2DM. Five-week-old non-diabetic Long-Evans Tokushima Otsuka (LETO) and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into normobaric (LETO-NB and OLETF-NB) and mild hyperbaric oxygen (LETO-MHO and OLETF-MHO) groups. The LETO-MHO and OLETF-MHO groups received 1266 hPa with 36% oxygen for 3 h daily for 22 weeks. Fasting and non-fasting blood glucose, HbA1c, and triglyceride levels were lower in the OLETF-MHO group than in the OLETF-NB group (P < 0.05). In the soleus muscle, peroxisome proliferator-activated receptor δ/β (Pparδ/β), Pparγ, and PPARγ coactivator-1α (Pgc-1α) mRNA levels were lower in the OLETF-NB group than in all other groups (P < 0.05), whereas myogenin (Myog) and myogenic factor 5 (Myf5) mRNA levels were higher in the OLETF-MHO group than in the LETO-NB and OLETF-NB groups (P < 0.05). The soleus muscles in the OLETF-NB group contained only low-oxidative Type I fibers, whereas those in all other groups contained high-oxidative Type IIA and Type IIC fibers in addition to Type I fibers. Exposure to mild hyperbaric oxygen inhibits the decline in skeletal muscle oxidative capacity and prevents the hyperglycemia associated with T2DM. Pgc-1α, Myog, and Myf5 mRNA levels appear to be closely associated with skeletal muscle oxidative capacity in rats with T2DM.

Apoptosis In Recovering Human Skeletal Muscle after High Intensity Cycling In Men Receiving Ergogenic Rg1 Compound

PURPOSE: To examine the impact of high intensity exercise on cell death in human skeletal muscle during recovery with Rg1 supplementation, which has been shown to increase endurance performance. METHODS: Using randomized double blind placebo controlled crossover design, twelve young men were studied on three occasions: Placebo, Rg1 (1 mg) and Rg1 (5 mg) supplementation 1 h prior to a high-intensity exercise. Biopsied samples were taken from vastus lateralis before, immediately after and 3 h after a 1-h cycling exercise at 75% VO2max. RESULTS: Apoptotic and necrotic cells in vastus lateralis increased immediately after 1 h cycling (80-140% and 80-120%, P < 0.05), concurrent with macrophage infiltration (both CD68+ and CD163+). Increases in iNOS and myogenic factor Myf5 mRNA levels after exercise were further elevated during Rg1 supplemented trial. Rg1 (5 mg) significantly increased high intensity endurance performance and accelerates the disappearance of apoptotic and necrotic cell number occurred 3 h after exercise during recovery. CONCLUSION: High intensity exercise increased cell death in human skeletal muscle after high intensity aerobic exercise. The ergogenic compound Rg1 accelerates phagocytosis to remove unhealthy muscle cell in exercised skeletal muscle.

Pulsed low-level infrared laser alters mRNA levels from muscle repair genes dependent on power output in Wistar rats

Satellite cells are present in skeletal muscle functioning in the repair and regeneration of muscle injury. Activation of these cells depends on the expression of myogenic factor 5 (Myf5), myogenic determination factor 1(MyoD), myogenic regulatory factor 4 (MRF4), myogenin (MyoG), paired box transcription factors 3 (Pax3), and 7 (Pax7). Low-level laser irradiation accelerates the repair of muscle injuries. However, data from the expression of myogenic factors have been controversial. Furthermore, the effects of different laser beam powers on the repair of muscle injuries have been not evaluated. The aim of this study was to evaluate the effects of low-level infrared laser at different powers and in pulsed emission mode on the expression of myogenic regulatory factors and on Pax3 and Pax7 in injured skeletal muscle from Wistar rats. Animals that underwent cryoinjury were divided into three groups: injury, injury laser 25 Mw, and injury laser 75 mW. Low-level infrared laser irradiation (904 nm, 3 J cm−2, 5 kHz) was carried out at 25 and 75 mW. After euthanasia, skeletal muscle samples were withdrawn and the total RNA was extracted for the evaluation of mRNA levels from the MyoD, MyoG, MRF4, Myf5, Pax3, and Pax7 gene. Pax 7 mRNA levels did not alter, but Pax3 mRNA levels increased in the injured and laser-irradiated group at 25 mW. MyoD, MyoG, and MYf5 mRNA levels increased in the injured and laser-irradiated animals at both powers, and MRF4 mRNA levels decreased in the injured and laser-irradiated group at 75 mW. In conclusion, exposure to pulsed low-level infrared laser, by power-dependent effect, could accelerate the muscle repair process altering mRNA levels from paired box transcription factors and myogenic regulatory factors.

Strength training prior to muscle injury potentiates low-level laser therapy (LLLT)-induced muscle regeneration.

We evaluated whether strength training (ST) performed prior to skeletal muscle cryolesion would act as a preconditioning, improving skeletal muscle regeneration and responsiveness to low-level laser therapy (LLLT). Wistar rats were randomly assigned into non-exercised (NE), NE plus muscle lesion (NE + LE), NE + LE plus LLLT (NE + LE + LLLT), strength training (ST), ST + LE, and ST + LE + LLLT. The animals performed 10weeks of ST (climbing ladder; 3× week; 80% overload). Forty-eight hours after the last ST session, tibialis anterior (TA) cryolesion was induced and LLLT (InGaAlP, 660nm, 0.035W, 4.9J/cm2/point, 3 points, spot light 0.028cm2, 14J/cm2) initiated and conducted daily for 14 consecutive days. The difference between intergroups was assessed using Student's t test and intragroups by two-way analysis of variance. Cryolesion induced massive muscle degeneration associated with inflammatory infiltrate. Prior ST improved skeletal regeneration 14-days after cryolesion and potentiated the regenerative response to LLLT. Cryolesion induced increased TNF-α levels in both NE + LE and ST + LE groups. Both isolated ST and LLLT reduced TNF-α to control group levels; however, prior ST potentiated LLLT response. Both isolated ST and LLLT increased IL-10 levels with no additional effect. In contrast, increased TA IL-6 levels were restricted to ST and ST + LE + LLLT groups. TA myogenin mRNA levels were not changed by neither prior ST or ST + LLLT. Both prior ST and LLLT therapies increased MyoD mRNA levels and, interestingly, combined therapies potentiated this response. Myf5 mRNA levels were increased only in ST groups. Taken together, our data provides evidences for prior ST potentiating LLLT efficacy in promoting skeletal muscle regeneration.

Effects of Dimethyl Sulphoxide and Dexamethasone on mRNA Expression of Myogenesis- and Muscle Proteolytic System-related Genes in Mouse Myoblastic C2C12 Cells

We examined the time course of mRNA expression of myogenic cell differentiation- and muscle proteolytic system-related genes in cultures of C2C12 cells during differentiation from myoblasts to myotubes. Furthermore, we treated C2C12 myotubes with dimethyl sulphoxide (DMSO) and dexamethasone (Dex), and examined changes in these mRNA levels. Myogenin (Myog), Atrogin1, forkhead box O1 (Foxo1) and Capn1 mRNA levels increased in C2C12 cells differentiating from myoblasts to myotubes, whereas Myf5 mRNA levels decreased. Although genes such as MRF4, Foxo3a, UbB, Capn1 and MuRF1 mRNAs in the myotubes were affected by DMSO exposure, mRNA levels of other genes were not markedly affected by exposure to 0.02% or 0.5% DMSO. Myf5, MRF4, Atrogin1, Foxo3 and MuRF1 mRNA levels were elevated by Dex at all time points, Cbl and Capn1 mRNA levels were significantly elevated by Dex at 8 h, and Myog mRNA levels were significantly elevated by Dex at 24 h. However, CtsH mRNA levels decreased significantly with Dex at 24 h. This study provides a useful database of gene profiles that are differentially expressed throughout myogenic cell differentiation and the muscle proteolytic system.

CMF1–Rb interaction promotes myogenesis in avian skeletal myoblasts

CMF1 protein is expressed in developing striated muscle before the expression of contractile proteins, and depletion of CMF1 in myoblasts results in inability to express muscle-specific proteins. Previous studies of CMF1 identify a functional Rb-binding domain, which is conserved in the murine and human homologues. Here, we show that CMF1 binds Rb family members, while a CMF1 protein with deletion of the Rb-binding domain (Rb-del CMF1) does not. Myogenic cell lines over-expressing Rb-del CMF1 proliferate normally, but exhibit markedly impaired differentiation, including dramatically reduced contractile proteins gene expression and failure to fuse into myotubes. Furthermore, by quantitative real-time polymerase chain reaction, MyoD and Myf5 mRNA levels are comparable to wild-type, while myogenin and contractile protein mRNA levels are significantly attenuated. These data demonstrate that CMF1 regulates myocyte differentiation by interaction with Rb family members to induce expression of myogenic regulatory factors.

Temperature and the expression of myogenic regulatory factors (MRFs) and myosin heavy chain isoforms during embryogenesis in the common carpCyprinus carpioL.

Embryos of the common carp, Cyprinus carpio L., were reared from fertilization of the eggs to inflation of the swim bladder in the larval stage at 18 and 25 degrees C. cRNA probes were used to detect transcripts of the myogenic regulatory factors MyoD, Myf-5 and myogenin, and five myosin heavy chain (MyHC) isoforms during development. The genes encoding Myf-5 and MyoD were switched on first in the unsegmented mesoderm, followed by myogenin as the somites developed. Myf-5 and MyoD transcripts were initially limited to the adaxial cells, but Myf-5 expression spread laterally into the presomitic mesoderm before somite formation. Two distinct bands of staining could be seen corresponding to the cellular fields of the forming somites, but as each furrow delineated, Myf-5 mRNA levels declined. Upon somite formation, MyoD expression spread laterally to encompass the full somite width. Expression of the myogenin gene was also switched on during somite formation, and expression of both transcripts persisted until the somites became chevron-shaped. Expression of MyoD was then downregulated shortly before myogenin. The expression patterns of the carp myogenic regulatory factor (MRF) genes most-closely resembled that seen in the zebrafish rather than the rainbow trout (where expression of MyoD remains restricted to the adaxial domain of the somite for a prolonged period) or the herring (where expression of MyoD persists longer than that of myogenin). Expression of two embryonic forms of MyHC began simultaneously at the 25-30 somite stage and continued until approximately two weeks post-hatch. However, the three adult isoforms of fast muscle MyHC were not detected in any stage examined, emphasizing a developmental gap that must be filled by other, as yet uncharacterised, MyHC isoform(s). No differences in the timing of expression of any mRNA transcripts were seen between temperature groups. A phylogenetic analysis of the MRFs was conducted using all available full-length amino acid sequences. A neighbour-joining tree indicated that all four members evolved from a common ancestral gene, which first duplicated into two lineages, each of which underwent a further duplication to produce Myf-5 and MyoD, and myogenin and MRF4. Parologous copies of MyoD from trout and Xenopus clustered closely together within clades, indicating recent duplications. By contrast, MyoD paralogues from gilthead seabream were more divergent, indicating a more-ancient duplication.

Myf-5 Is Transiently Expressed in Nonmuscle Mesoderm and Exhibits Dynamic Regional Changes within the Presegmented Mesoderm and Somites I–IV

Myf-5 is one of four myogenic regulatory factors that play important roles in skeletal muscle development. This study provides detailed analysis of Myf-5 expression during early chick development using an in situ hybridization technique that has been optimized to detect low level Myf-5 transcripts. This facilitated detection of heretofore unrecognized dynamic changes in Myf-5 expression patterns. Myf-5 expression is first detected at stage 3 in the primitive streak and exhibits transient low-level expression in nonmyogenic mesoderm. Myf-5 is later expressed in the presegmented mesoderm (psm) in a reiterating pattern that is coordinated with somitogenesis and also colocalizes with the Notch ligand C-Delta-1. In somites (S) I–IV, Myf-5 expression exhibits dynamic regional changes, and in somites rostral to S IV, Myf-5 is expressed at higher levels in muscle precursors in the dorsomedial somite. Semiquantitative comparison of Myf-5 mRNA levels in the psm and in myotome-containing somites indicates about a 10-fold difference. The expression pattern of Myf-5 differs from that of MyoD, which we find is expressed only in the dorsomedial somite. These data reveal that Myf-5 is expressed at low levels several stages before muscle differentiation occurs and suggest that only a subset of cells that initially express Myf-5 will upregulate its expression and differentiate as muscle.

A calcineurin- and NFAT-dependent pathway regulates Myf5 gene expression in skeletal muscle reserve cells.

Myf5 is a member of the muscle regulatory factor family of transcription factors and plays an important role in the determination, development, and differentiation of skeletal muscle. However, factors that regulate the expression and activity of Myf5 itself are not well understood. Recently, a role for the calcium-dependent phosphatase calcineurin was suggested in three distinct pathways in skeletal muscle: differentiation, hypertrophy, and fiber-type determination. We propose that one downstream target of calcineurin and the calcineurin substrate NFAT in skeletal muscle is regulation of Myf5 gene expression. For these studies, we used myotube cultures that contain both multinucleated myotubes and quiescent, mononucleated cells termed 'reserve' cells, which share many characteristics with satellite cells. Treatment of such myotube cultures with the calcium ionophore ionomycin results in an approximately 4-fold increase in Myf5 mRNA levels, but similar effects are not observed in proliferating myoblast cultures indicating that Myf5 is regulated by different pathways in different cell populations. The increase in Myf5 mRNA levels in myotube cultures requires the activity of calcineurin and NFAT, and can be specifically enhanced by overexpressing the NFATc isoform. We used immunohistochemical analyses and fractionation of the cell populations to demonstrate that the calcium regulated expression of Myf5 occurs in the mononucleated reserve cells. We conclude that Myf5 gene expression is regulated by a calcineurin- and NFAT-dependent pathway in the reserve cell population of myotube cultures. These results may provide important insights into the molecular mechanisms responsible for satellite cell activation and/or the renewal of the satellite cell pool following activation and proliferation.

Neural and hormonal control of expression of myogenic regulatory factor genes during regeneration of Xenopus fast muscles: myogenin and MRF4 mRNA accumulation are neurally regulated oppositely.

With the aim to investigate the influence of both innervation and thyroid hormone, on the expression of the MRFs during muscle regeneration, we performed cardiotoxin injury-induced regeneration experiments on fast muscles of adult Xenopus laevis subjected to different experimental conditions, including denervation and T3 treatment, and analyzed the accumulation of the four myogenic regulatory factors (MRFs) using RT-PCR and in situ hybridization. We show here that manipulation of hormone levels or innervation resulted in differential alterations of MRF expression. Denervation and T3 treatment transiently down-regulated Myf-5 mRNA levels at the beginning of the regeneration process. Myf-5 was the only myogenic factor subject to thyroid hormone influence. Muscle denervation persistently reduces the levels of MRF4 transcripts as early as the first stages of regeneration, whereas the levels of myogenin mRNA were increased in the late stages of regeneration. This suggests that MRF4 expression may be induced by innervation and hence may be involved in mediating transcriptional responses to innervation and that myogenin expression may compensate for the down-regulation of MRF4 gene. This switch in MRF gene expression following denervation could have important consequences for the ability of Xenopus regenerating muscles to recover function after denervation.

Use of p112-deficient myoblasts to determine the temporal order of the in vitro expression of myogenic components.

The present investigation examines the function and site(s) of involvement of an ecto-protein kinase and its substrate protein (a cell surface 112 kDa protein) in the in vitro myogenic pathway. The phosphorylated 112 kDa protein (p112) has recently been shown to be involved in myogenesis. Not much information is currently available on the role of the ecto-protein kinase and the 112 kDa protein in modulating the expression of the myogenic factors and various muscle-specific proteins. Five different p112-deficient rat myoblasts were used to examine the temporal order of the in vitro expression of the myogenic components; namely, L6 myoblasts treated with BrdUrd or phloretin, a conditional p112-defective mutant (clone D1), an ecto-protein kinase-deficient mutant (clone F72), and a mutant defective in the 112 kDa protein (clone D1/S4). All these p112-deficient myoblasts were also impaired in myogenesis. The absence of p112, ecto-protein kinase, and/or the 112 kDa protein was found to have no effect on the Myf-5 mRNA level. However, the expected increase in NCAM and Myf-4 mRNAs was not observed in any of the p112-deficient myoblasts examined. This suggests that the p112 site of action is probably located upstream of the Myf-4 and NCAM sites in the myogenic pathway. While 7-28 fold increases in the MLC, MHC, and TnT transcripts were observed during myogenesis, such increases were not observed in the p112-deficient myoblasts. However, when mutant D1/S4 was transfected with the myf-4 cDNA, expression of Myf-4 in the transfectant resulted in increased level of the MLC, MHC, and TnT mRNAs, and in myotube formation, even though the Myf-5 and NCAM mRNA levels and p112 were not altered. This suggests that p112 may function by activating transcription of Myf-4, which will subsequently promote the expression of muscle-specific proteins and myotube formation. In the absence of p112, Myf-5 cannot activate the expression of Myf-4, NCAM, MLC, MHC, TnT, and myotube formation. If all these components are involved in the same myogenic pathway, then p112 may be acting downstream from Myf-5, and upstream from NCAM and Myf-4.

Paradoxical decrease in myf-5 messenger RNA levels during induction of myogenic differentiation by insulin-like growth factors.

Having previously demonstrated that the insulin-like growth factors (IGFs) induce expression of the myogenin gene, we have now extended our investigation of the induction of myogenesis by the IGFs to a second member of the MyoD family, myf-5. This is the only myogenesis gene other than myogenin expressed early in the differentiation of L6 myoblasts, so its regulation was of particular interest because of our observations on myogenin. In contrast to myogenin, myf-5 mRNA was detectable in proliferating myoblasts, but the steady state levels of myf-5 mRNA fell strikingly for 48 h after the cells were switched to low serum medium containing IGF-II in both murine cell lines and myoblasts cultured from human muscle. In spite of this decrease, translation of myf-5 mRNA appeared essential during the early stages of stimulation of myogenesis by the IGFs; an antisense oligodeoxynucleotide complementary to the first five codons of myf-5 blocked the increase in myogenin mRNA and inhibited morphological (cell fusion) and biochemical (creatine kinase elevation) aspects of myogenesis. We conclude that expression of myf-5 is essential for the initial induction of myogenin by the IGFs, but that subsequent elevation of myogenin expression is independent of myf-5, possibly resulting from autoinduction of the myogenin gene. The functional significance of the dramatic decrease in myf-5 mRNA levels during differentiation is not obvious.

Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development

The myogenic basic HLH transcription factor family of genes, composed of MyoD, myogenin, Myf-5, and Myf-6, are thought to regulate skeletal muscle differentiation. To understand the role of MyoD in myogenesis, we have introduced a null mutation of MyoD into the germline of mice. Surprisingly, mice lacking MyoD are viable and fertile. Histological examination of skeletal muscle failed to reveal any morphological abnormalities in these mice. Furthermore, Northern analysis revealed normal levels of skeletal muscle-specific mRNAs. Significantly, Myf-5 mRNA levels are elevated in postnatal mutant mice. Normally, Myf-5 expression becomes markedly reduced at day 12 of gestation when MyoD mRNA first appears. This suggests that Myf-5 expression is repressed by MyoD. Our results indicate that MyoD is dispensable for skeletal muscle development in mice, revealing some degree of functional redundancy in the control of the skeletal myogenic developmental program.