MUSCLE DIFFERENTIATION - INSULIN-LIKE GROWTH-FACTORS AS POSITIVE MODULATORS OF MYOGENIC REGULATORY GENES

The contribution of autocrine production of insulin-like growth factor II (IGFII) to myogenic differentiation was studied in the mouse myoge nic C2 cells. Permissive C2 cells were stably transfected with a vecto r generating antisense RNA complementary to IGF RNAs. Our results show that : (1) accumulation of IGFII mRNA is dramatically decreased (this mRNA is undetectable by RNA blotting) ; (2) accumulation of MyoD mRNA also becomes undetectable by RNA blot analysis ; (3) the ability of t he cells to differentiate, including the activation of myogenin and my osin genes, is severely compromised ; (4) expression of the MyoD genes and the ability to differentiate are restored following the addition of insulin or IGF to the cells. Our observations indicate that the aut onomous differentiation of myogenic cells requires 'autocrine producti on of IGF and raise the possibility that IGFII positively regulates ex pression of the MyoD gene, one of the members of the myogenic regulato ry factor family.