Ras is involved in nerve-activity-dependent regulation of muscle genes

Gene expression in skeletal muscle is regulated by the firing pattern of mo tor neurons, but the signalling systems involved in excitation-transcriptio n coupling are unknown. Here, using in vivo transfection in regenerating mu scle, we show that constitutively active pas and a Ras mutant that selectiv ely activates the MAPK(ERK) pathway are able to mimic the effects of slow m otor neurons on expression of myosin genes. Conversely, the effect of slow motor neurons is inhibited by a dominant-negative Has mutant. MAPK(ERK) act ivity is increased by innervation and by low-frequency electrical stimulati on. These results indicate that Ras-MAPK signalling is involved in promotin g nerve-activity-dependent differentiation of slow muscle fibres in vivo.