Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized 
by loss of motor neurons, denervation of target muscles, muscle atrophy, and 
paralysis. Understanding ALS pathogenesis may require a fuller understanding of 
the bidirectional signaling between motor neurons and skeletal muscle fibers at 
neuromuscular synapses. Here, we show that a key regulator of this signaling is 
miR-206, a skeletal muscle-specific microRNA that is dramatically induced in a 
mouse model of ALS. Mice that are genetically deficient in miR-206 form normal 
neuromuscular synapses during development, but deficiency of miR-206 in the ALS 
mouse model accelerates disease progression. miR-206 is required for efficient 
regeneration of neuromuscular synapses after acute nerve injury, which probably 
accounts for its salutary effects in ALS. miR-206 mediates these effects at 
least in part through histone deacetylase 4 and fibroblast growth factor 
signaling pathways. Thus, miR-206 slows ALS progression by sensing motor neuron 
injury and promoting the compensatory regeneration of neuromuscular synapses.