Actin Remodeling in Skeletal Myogenesis from Nuclear Signaling to Myoblast Fusion

Actin remodeling accompanies myoblast proliferation, lineage commitment, elongation, fusion, and myofibril assembly, but these changes do not constitute a single linear pathway. This review separates three experimentally distinguishable scales of actin function in skeletal myogenesis. First, the balance between monomeric and filamentous actin controls myocardin-related transcription factor–serum response factor (MRTF–SRF) signaling and thereby couples cytoskeletal state to gene expression. Second, integrin–focal adhesion kinase (FAK)–Rho signaling and actomyosin tension influence Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) activity, with outcomes that depend on cell state, density, mechanical context, and the non-equivalent functions of YAP and TAZ. Third, spatially restricted actin-related protein 2/3 (Arp2/3)-dependent branched actin networks generate protrusive force at the fusogenic synapse, while a mechanically reinforced receiving-cell cortex provides counterforce and cooperates with membrane fusogens to form and enlarge fusion pores. We compare evidence from cultured myoblasts, developmental models, and adult muscle regeneration, with attention to what each assay measures. We propose that bulk actin abundance, filament turnover, mechanical tension, and local actin architecture should be treated as separate variables. This framework reconciles apparently conflicting results and identifies experiments that can distinguish correlation from causal actin-to-nucleus signaling during muscle formation and repair.