Muscle ciliary neurotrophic factor receptor α contributes to motor neuron STAT 3 activation following peripheral nerve lesion

Expression of the ciliary neurotrophic factor ( CNTF ) receptor essential ligand binding subunit, CNTF receptor α ( CNTFR α), is induced in motor neurons and skeletal muscle following peripheral nerve lesion. We previously found muscle CNTFR α promotes motor neuron axon regeneration post‐lesion. Both nerve lesion and CNTF administration activate motor neuron signal transducer and activator of transcription 3 ( STAT 3), a transcription factor implicated in axon growth, suggesting CNTF receptors may contribute to the lesion‐induced STAT 3 activation. However, many receptor types signal through STAT 3, and if CNTF receptors contribute, motor neuron receptors seemed most likely to regulate motor neuron STAT 3. To determine the role played by muscle CNTFR α, we used in vivo, muscle‐specific CNTFR α depletion in mice and report here that this selectively impairs the second phase, sustained motor neuron STAT 3 activation post‐lesion. Thus, muscle CNTFR α makes an essential contribution to motor neuron STAT 3 activation during axon regeneration and may thereby promote axon regeneration through such signaling. We also report CNTFR α quantitative PCR suggesting involvement of many denervated muscle types, as well as muscle damaged at the lesion site. The present data add to the evidence suggesting that enhancing muscle CNTFR α expression may promote motor neuron regeneration in trauma and disease.