This paper characterizes changes in mRNA expression throughout myogenesis using high-intensity oligonucleotide arrays. Gene clusters involved in muscle contraction, cell adhesion, extracellular matrix function, cellular metabolism, mitochondrial transport, DNA replication, cell cycle control, mRNA transcription and immune regulation were all found to significantly increase.
This paper gives a comprehensive description of the events that occur over the course of skeletal myogenesis and the signalling pathways that regulate them. It also offers a comparison of in vivo and in vitro processes.
This article summarizes skeletal myogenesis, with a particular focus on molecular regulation. The authors also describe differences between embryonic and regenerative (adult) myogenesis.
This paper aims to determine if myogenin shares certain functions with either MyoD or Myf-5 in vivo. They used mice with double homozygous null mutations in the genes encoding MyoD and myogenin or Myf-5 and myogenin. The knockout of myogenin with these MRFs showed no additional muscle defects, indicating that myogenin's functional role is separate from the roles of MyoD and Myf-5.
This article explores the scope of genes that MyoD regulates throughout myogenic differentiation. The authors performed expression arrays and chromatin immunoprecipitation assays to show that myogenesis has subprograms of gene expression that are regulated by MyoD. They demonstrate that MyoD binds to the regulatory regions of all the muscle genes studied, whether expressed in early or late myogenesis.
This paper investigated the mRNA and protein expression along with the subcellular localization of various myogenic regulatory factors (MRFs) in C2C12 cells. This allowed the researchers to determine whether post-transcriptional and post-translational mechanisms are involved in the regulation of these MRFs.
This review article summarizes the structure and function of the myogenic regulatory factors MyoD, Myogenin, Myf5, and MRF4. The authors also explore the roles that each of these factors play in regulating both prenatal and postnatal (regenerative) myogenesis.
This paper looks at the molecular mechanisms regulating expression of MyHC isoforms in different muscle fiber types. They identified elements that regulate the expression of adult fast MyHC genes. Their results show that expression of MyoD/Myf-5 preferentially activate type IIb promotor and NFAT or calcineurin preferentially activated type IIa promotor.
This paper studies the gene expression of six myosin heavy chain (MyHC) isoforms across myogenesis in C2C12 cells. To study the unique isoforms they use RT-qPCR and compare this to total cDNA to determine relative gene expression. The researchers discovered that all six MyHC isoforms changed significantly across myogenesis, however, in two distinct groups. MyHC I, embryonic and neonatal isoforms were expressed early in differentiation, peaking at day 2 or 4 and decreasing afterward. MyHC IIa, IIx and IIb were expressed later and continued to increase to day 8.
This study uses high-resolution gel electrophoresis technique with western blotting to characterize MyHC composition in different mouse skeletal muscles. All muscles studied showed a transition from emb and neo isofroms to adult MyHC isoforms (Type I, Type IIa, IIx and IIb). Interestingly, they find that different muscles show distinct MyHC isoform transitions.
This study challenges the idea that the mitogens in high serum concentration totally inhibit myogenic differentiation. C2C12 myoblasts were shown to differentiate to a greater extent in serum rich conditions than serum deprived conditions. It was postulated that an autocrine/ paracrine feedback loop overcomes the inhibitory activity of serum mitogens are permits differentiation.
This article shows cell-cell communication during myogenesis is necessary, and myogenic differentiation and cell cycle withdrawal markers are expressed in a cell density-dependent manner.
This review paper outlines the importance of cell–cell contact-dependent signaling in myogenesis. The authors describe how commitment of progenitor cells to the skeletal muscle lineage, postnatal growth of fibers by recruitment of myoblasts to sites of fusion, and fiber-type patterning are each regulated through cell–cell contact between various non-muscle and muscle cell types.