MyoD protein is differentially accumulated in fast and slow skeletal muscle fibres and required for normal fibre type balance in rodents

Abstract

MyoD is a muscle-specific transcription factor involved in commitment of cells to myogenesis. MyoD mRNA levels differ between fast and slow muscles, suggesting that MyoD may regulate aspects of fibre type. Here we show that detectable MyoD protein becomes restricted during development to the nuclei of the fastest classes of fibres in fast muscles. myoDm1 mice, in which the myoD gene has been disrupted, show subtle shifts in fibre type of fast muscles toward a slower character, suggesting that MyoD is involved in the maintenance of the fast IIB/IIX fibre type. In contrast, slow muscle shifts to a faster phenotype in myoDm1. Moreover, MD6.0-lacZ transgenic mice with the myoD promoter driving lacZ, show highest beta-galactosidase activity in the fastest fibres of fast muscles, but also express low levels in slow fibres of slow, but not fast, muscles, suggesting distinct regulation of gene expression in slow fibres of fast and slow muscles.

Satellite cells express distinct patterns of myogenic proteins in immature skeletal muscle

“…It is possible that Pax7 plays a role in establishing myonuclear fate or myofiber phenotype in postnatal muscle. Similarly, myonuclear MyoD expression suggests a role in postnatal myofiber regulation, but the similar number of MyoD-positive myonuclei in the EDL and soleus muscles does not agree with previously reported muscle-specific differences in mRNA levels (Hughes et al, 1993(Hughes et al, , 1997Voytik et al, 1993) where the soleus has higher levels of myogenin and the EDL higher levels of MyoD. It should be noted that there is a major difference in the techniques used in the current studies compared with previous studies (Hughes et al, 1993(Hughes et al, , 1997Voytik et al, 1993), because the current study compared the number of nuclei expressing each factor, whereas the previous study compared total RNA or protein between muscles.…”

“…Similarly, myonuclear MyoD expression suggests a role in postnatal myofiber regulation, but the similar number of MyoD-positive myonuclei in the EDL and soleus muscles does not agree with previously reported muscle-specific differences in mRNA levels (Hughes et al, 1993(Hughes et al, , 1997Voytik et al, 1993) where the soleus has higher levels of myogenin and the EDL higher levels of MyoD. It should be noted that there is a major difference in the techniques used in the current studies compared with previous studies (Hughes et al, 1993(Hughes et al, , 1997Voytik et al, 1993), because the current study compared the number of nuclei expressing each factor, whereas the previous study compared total RNA or protein between muscles. Protein and mRNA levels for a single factor do not appear to be directly related because of translational efficiency and post-translational modifications, which may explain the difference between previous work (Hughes et al, 1993(Hughes et al, , 1997Voytik et al, 1993) and the current study.…”

“…It should be noted that there is a major difference in the techniques used in the current studies compared with previous studies (Hughes et al, 1993(Hughes et al, , 1997Voytik et al, 1993), because the current study compared the number of nuclei expressing each factor, whereas the previous study compared total RNA or protein between muscles. Protein and mRNA levels for a single factor do not appear to be directly related because of translational efficiency and post-translational modifications, which may explain the difference between previous work (Hughes et al, 1993(Hughes et al, , 1997Voytik et al, 1993) and the current study. The discovery of MyoD-and myogenin-positive cells in the interstitial space also corresponds to the results of previous studies (Tamaki et al, 2002a,b).…”

Differences in the Function of Three Conserved E-boxes of the Muscle Creatine Kinase Gene in Cultured Myocytes and in Transgenic Mouse Skeletal and Cardiac Muscle

“…For example, bovine muscles that are abundant in slow and intermediate myosin heavy chains have more Myf5 than do muscles with faster myosin heavy chains (67). MyoD has been reported to be highest in the fastest muscle fibers in mouse (68,69), whereas myogenin has been reported to be high in slow muscles (70). MRF4 has been suggested as important in maintaining the slow muscle phenotype (71,72), which makes identification of an enhancer in its upstream region with specificity for fast fibers (as mentioned above; Ref.…”

Neuronal control of myogenic regulatory factor accumulation in fetal muscle

“…myoD and myogenin mRNAs are preferentially expressed in adult rodent fast and slow twitch muscle fibers, respectively; however, there does not appear to be an absolute correlation between the accumulation of myoD and myogenin mRNAs and specific fiber types (Hughes et al, 1993(Hughes et al, , 1997Voytik et al, 1993;Kraus and Pette, 1997). Denervation of adult, rodent hindlimb muscles results in large increases in the mRNAs for all of the MRFs by ϳ2 days after denervation (Duclert et al, 1991;Eftimie et al, 1991;Witzemann and Sakmann, 1991;Buonanno et al, 1992;Voytik et al, 1993;Hyatt et al, 2003), followed almost immediately by increases in myoD, myogenin, and MRF4 proteins (Weis, 1994;Weis et al, 2000;Kostrominova et al, 2000;Hyatt et al, 2003;Ishido et al, 2004).…”