title: Heterogeneous activation of a slow myosin gene in proliferating myoblasts and differentiated single myofibers.
abstract: Each skeletal muscle contains a fixed ratio of fast and slow myofibers that are distributed in a stereotyped pattern to achieve a specific motor function. How myofibers are specified during development and regeneration is poorly understood. Here we address this question using transgenic reporter mice that indelibly mark the myofiber lineages based on activation of fast or slow myosin. Lineage tracing indicates that during development all muscles have activated the fast myosin gene Myl1, but not the slow myosin gene Myh7, which is activated in all slow but a subset of fast myofibers. Similarly, most nascent myofibers do not activate Myh7 during fast muscle regeneration, but the ratio and pattern of fast and slow myofibers are restored at the completion of regeneration. At the single myofiber level, most mature fast myofibers are heterogeneous in nuclear composition, manifested by mosaic activation of Myh7. Strikingly, Myh7 is activated in a subpopulation of proliferating myoblasts that co-express the myogenic progenitor marker Pax7. When induced to differentiate, the Myh7-activated myoblasts differentiate more readily than the non-activated myoblasts, and have a higher tendency, but not restricted, to become slow myotubes. Together, our data reveal significant nuclear heterogeneity within a single myofiber, and challenge the conventional view that myosin genes are only expressed after myogenic differentiation. These results provide novel insights into the regulation of muscle fiber type specification.
authors: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors: Jing-Hua
authors: JH
authors: Wang
authors: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors: Qiao-Jing
authors: QJ
authors: Wang
authors: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors: Chao
authors: C
authors: Wang
authors: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors: Brad
authors: B
authors: Reinholt
authors: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors: Alan L
authors: AL
authors: Grant
authors: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors: David E
authors: DE
authors: Gerrard
authors: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA. Electronic address: skuang@purdue.edu.
authors: Shihuan
authors: S
authors: Kuang
mesh_terms: D000818:Animals; D054715:Cardiotoxins / Q000737:chemistry; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D032446:Myoblasts / Q000166:cytology*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry; D051763:PAX7 Transcription Factor / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology
chemical_list: D054715:Cardiotoxins; C551613:Myh7 protein, mouse; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D049452:Green Fluorescent Proteins; D018995:Myosin Heavy Chains; D009218:Myosins
keywords: Cre/LoxP; Muscle fiber type; Myogenesis; Regeneration; Satellite cells