ABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
Fusion of myoblasts into multinucleated myofibers is crucial for skeletal muscle development and regeneration. However, the mechanisms controlling this process remain to be determined. Here we identified the involvement of a new extracellular matrix protein in myoblast fusion. Collagen XXV is a transmembrane-type collagen highly transcribed during early myogenesis when primary myofibers form. Limb muscles of E12.5 and E14.5 Col25a1-/- embryos show a clear defect in the formation of multinucleated myofibers. In cell culture, the cleaved soluble extracellular domain of the collagen XXV is sufficient to promote the formation of highly multinucleated myofibers. Col25a1 is transiently expressed during myogenic differentiation and Col25a1 transcripts are down-regulated in multinucleated myofibers by a muscle-specific microRNA, miR-499. Altogether, these findings indicate that collagen XXV is required in vivo and in vitro for the fusion of myoblasts into myofibers and give further evidence that microRNAs participate to the regulation of this process.
Subject(s)
Cell Differentiation , Muscle Development , Non-Fibrillar Collagens/metabolism , 3' Untranslated Regions , Animals , Base Sequence , Cells, Cultured , Embryo, Mammalian/cytology , Embryo, Mammalian/metabolism , Humans , Mice , Mice, Knockout , MicroRNAs/chemistry , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle, Skeletal/metabolism , Myoblasts/cytology , Myoblasts/metabolism , Non-Fibrillar Collagens/deficiency , Non-Fibrillar Collagens/genetics , Rats , Sequence AlignmentABSTRACT
Following injury, skeletal muscles can regenerate from muscle specific stem cells, called satellite cells. Quiescent in uninjured muscles, satellite cells become activated, proliferate and differentiate into myotubes. Muscle regeneration occurs following distinct main overlapping phases, including inflammation, regeneration and maturation of the regenerated myofibers. Each step of muscle regeneration is orchestrated through complex signaling networks and gene regulatory networks, leading to the expression of specific set of genes in each concerned cell type. Apart from the well-established transcriptional mechanisms involving the myogenic regulatory factors of the MyoD family, increasing data indicate that each step of muscle regeneration is controlled by a wide range of non-coding RNAs. In this review, we discuss the role of two classes of non-coding RNAs (microRNAs and long non-coding RNAs) in the inflammatory, regeneration and maturation steps of muscle regeneration.
