Adult skeletal muscles comprise a large number of fibres, with different morphological, contractile and biochemical properties. Myosin heavy chain (MHC) isoforms play a key role in determining muscle mechanical properties, and in parallel with energy metabolism determinants, account for muscle phenotype. The expression of MHC isoforms is under the control of a number of external factors such as neuromuscular activity, mechanical loading and altered motoneuron impulse patterns. Although skeletal muscle adapts to altered functional demand, myofibres exhibit a limited capacity to changes in MHC expression, supporting the concept of a limited adaptive range of myofibre transitions. Skeletal myogenesis results from a well-established sequence of cellular events, which involves several waves of formation of myotubes from distinct muscle cell precursors. Then, in addition to its phenotypic heterogeneity, skeletal muscle diversity also results from the heterogeneity muscle cell precursors. It has been previously suggested that the existence of distinct populations of myoblasts may at least partly, explain the limited range of muscle plasticity. In contrast to adult muscle, regenerated muscle comprises myofibres arising from a homogeneous population of muscle cell precursors, namely satellite cells. Then, studying the response of regenerated skeletal muscle to factors known to control muscle phenotype allows examining whether the existence of discrete populations of early myogenic cells plays a role in the extent of muscle plasticity (Bigard et al, 1999). There are experimental evidences that regenerated slow-twitch muscles demonstrate a more complete and more marked response than intact non-injured muscles to removal of weight-bearing activity. Similarly, the developmental history of myofibres could play a role in the adaptability of skeletal muscle to motor innervation, increase in functional load (Bigard et al, 2001) and endurance training (Bigard et al, 1999, 2000). Moreover, regenerated muscles showed a higher responsiveness to calcineurin inhibition through prolonged cyclosporin (CsA) administration (Koulmann et al, 2006). However, this higher plasticity of regenerated muscle seemed to be restricted to adaptive responses of MHC expression (Bigard et al, 2000 ; Zoll et al, 2001). Taken together, these findings are consistent with the concept that the myogenic lineage may account for the extent of muscle plasticity. The distinct embryonic origin of muscle satellite cells contributes to explain, at least partly, the high responsiveness of regenerated muscles to changes in muscle functional load.