Fig. 1

Myogenesis is a multi-step process regulated by a cascade of transcription factors. A Lineage specification of progenitors under the influence of Pax3/7 precedes expression of muscle regulatory factors (MyoD and Myf5), which commit cells and begin muscle differentiation by promoting expression of Mrf4 and Myogenin. Myoblasts, originating from the mesoderm, enter the cell cycle and proliferate. Upon withdrawal of growth factors, proliferating myoblasts exit the cell cycle and begin to differentiate: Myogenin and MRF4 are crucial in this step promoting elongation and fusion with neighbouring cells to form multinucleated myotubes. The myotubes begin to express muscle-specific proteins, such as cytoskeletal proteins (including sarcomeric myosin and α-actin), muscle creatine kinase (MCK) and ryanodine receptor 1. Mature muscle contains myofibres and a subset of progenitors forming the quiescent satellite cell niche, which can be activated for muscle regeneration. B Phase contrast images of C2C12 myoblasts (left) and myotubes differentiated to 7 days (right). C RYR1 immunocytochemistry with nuclear stain DAPI in C2C12 differentiated into myotubes at 8 days of serum starvation – note these are not organised as in mature myofibres. (Scale bar represents 50 μm). Created in BioRender.com