title: Comparative expression profiling identifies differential roles for Myogenin and p38α MAPK signaling in myogenesis.
abstract: Skeletal muscle differentiation is mediated by a complex gene expression program requiring both the muscle-specific transcription factor Myogenin (Myog) and p38α MAPK (p38α) signaling. However, the relative contribution of Myog and p38α to the formation of mature myotubes remains unknown. Here, we have uncoupled the activity of Myog from that of p38α to gain insight into the individual roles of these proteins in myogenesis. Comparative expression profiling confirmed that Myog activates the expression of genes involved in muscle function. Furthermore, we found that in the absence of p38α signaling, Myog expression leads to the down-regulation of genes involved in cell cycle progression. Consistent with this, the expression of Myog is sufficient to induce cell cycle exit. Interestingly, p38α-defective, Myog-expressing myoblasts fail to form multinucleated myotubes, suggesting an important role for p38α in cell fusion. Through the analysis of p38α up-regulated genes, the tetraspanin CD53 was identified as a candidate fusion protein, a role confirmed both ex vivo in primary myoblasts, and in vivo during myofiber regeneration in mice. Thus, our study has revealed an unexpected role for Myog in mediating cell cycle exit and has identified an essential role for p38α in cell fusion through the up-regulation of CD53.
authors: Sprott Center for Stem Cell Research, Regenerative Medicine Program,  Ottawa Hospital Research Institute, Ottawa, ON,  Canada K1H 8L6.
authors: Qi-Cai
authors: QC
authors: Liu
authors: Xiao-Hui
authors: XH
authors: Zha
authors: Hervé
authors: H
authors: Faralli
authors: Hang
authors: H
authors: Yin
authors: Caroline
authors: C
authors: Louis-Jeune
authors: Eusebio
authors: E
authors: Perdiguero
authors: Erinija
authors: E
authors: Pranckeviciene
authors: Pura
authors: P
authors: Muñoz-Cànoves
authors: Michael A
authors: MA
authors: Rudnicki
authors: Marjorie
authors: M
authors: Brand
authors: Carol
authors: C
authors: Perez-Iratxeta
authors: F Jeffrey
authors: FJ
authors: Dilworth
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002459:Cell Fusion; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics* / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics* / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000502:physiology*; D018008:Myogenin / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D060265:Tetraspanin 25 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C554895:Cd53 protein, mouse; D035683:MicroRNAs; C532375:Mirn20 microRNA, mouse; C503801:Myog protein, mouse; D018008:Myogenin; D060265:Tetraspanin 25; D048308:Mitogen-Activated Protein Kinase 14