MYOGENIC DIFFERENTIATION TRIGGERED BY ANTISENSE ACIDIC FIBROBLAST GROWTH-FACTOR RNA

Acidic fibroblast growth factor (FGF) and related family members regul ate differentiation in organisms as diverse as Xenopus laevis and mamm als. We utilized a well-characterized model of myogenic development to directly assess the importance of endogenously produced FGF in contro lling differentiation. A role for endogenous FGF is suggested by the p revious finding that acidic and basic FGF abundance in cultured myocyt es decreases during differentiation. In this study we inhibited the en dogenous production of FGF in murine Sol 8 myoblasts by using antisens e RNA and observed precocious myogenic differentiation. Exogenously su pplied acidic FGF rescues this phenotype. Further results suggest that the effect of FGF on myogenic differentiation is mediated in part thr ough inhibition of myogenin expression. These results demonstrate a di rect role for endogenously synthesized growth factors in regulating my ogenesis and provide support for a general role for related proteins i n mammalian development.