Figure 1

Model for the development, activation, and maintenance of the satellite cell. Upon skeletal muscle injury, quiescent satellite cells expressing Pax-7 and Foxk1 are activated to proliferate, up-regulating the myogenic determination factors, MyoD and Myf-5 [13–17], the myoblast marker desmin [16, 79], and Wnts 5a and 5b [12]. Satellite cell activation is regulated by the Notch signaling pathway [25], and proliferation is stimulated by a number of growth factors, including basic FGF, insulin-like growth factor-1, and HGF/SF [26, 32, 80]. Transition from proliferation to differentiation, which is accompanied by the down-regulation of Pax-7 [57] and up-regulation of Myogenin and MRF-4 [13, 14, 16], is dependent on both MyoD [36] and the Foxk1 pathway [33, 34]. Candidate satellite cell progenitors, which must activate Pax-7 for satellite cell development [57], include embryonic myoblast precursors, fetal myoblasts, and vessel-associated mesoangioblasts, the latter of which exhibits strong myogenic potential [60–62]. Additionally, bone marrow-derived (BMD) stem cells can contribute directly to quiescent satellite cells and regenerating muscle fibers following injury [54, 65, 68], and muscle SP cells have been used with some success in myoblast transplantation experiments into dystrophic muscle [53, 54]. Importantly, members of the Wnt family of secreted glycoproteins can convert SP cells favoring the hematopoietic fate into highly myogenic cells [12].