INSERM UMRS 1124, 45 rue des Saints-Pères, F-75270, Paris cedex 06, France.
Institut Necker-Enfants Malades, Inserm, U1151, 14 rue Maria Helena Vieira Da Silva, CS 61431, Paris, F-75014, France.
Sci Rep. 2019 Apr 10;9(1):5878. doi: 10.1038/s41598-019-42296-6.
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.
成肌细胞融合形成多核肌纤维对于骨骼肌的发育和再生至关重要。然而，控制这一过程的机制仍有待确定。在这里，我们发现一种新的细胞外基质蛋白参与了成肌细胞融合。胶原 XXV 是一种跨膜型胶原，在初级肌纤维形成时的早期肌发生过程中高度转录。E12.5 和 E14.5 期 Col25a1-/- 胚胎的肢体肌肉在形成多核肌纤维时明显存在缺陷。在细胞培养中，胶原 XXV 的可切割可溶性细胞外结构域足以促进高度多核肌纤维的形成。Col25a1 在成肌分化过程中瞬时表达，并且肌肉特异性 microRNA，miR-499 下调多核肌纤维中的 Col25a1 转录物。总的来说，这些发现表明胶原 XXV 在体内和体外都需要将成肌细胞融合形成肌纤维，并进一步证明 microRNAs 参与了这一过程的调节。
