Tissue regeneration through stem cell activation and/or cell dedifferentiation is widely distributed across the animal kingdom. By comparison, regeneration in mammals is poor and this may reflect a limited dedifferentiation potential of mature cells. Because mammalian myotubes can dedifferentiate in the presence of newt blastema extract, the present study tested the dedifferentiation induction capability of the blastema from the teleost Sternopygus macrurus (SmBE). Our in vitro data showed that SmBE did not induce cell cycle reentry of myonuclei in myotubes. Instead, SmBE caused myotubes to detach and time-lapse imaging analyses characterized the cellular events before their detachment. Furthermore, SmBE enhanced myoblast proliferation and reversibly inhibited their differentiation. These data suggest the presence of protein factors in SmBE that regulate mammalian muscle physiology and differentiation, but do not support the conservation of a dedifferentiation induction capability by the blastema of S. macrurus. Developmental Dynamics 237:2830–2843, 2008. © 2008 Wiley-Liss, Inc.