Muscle and motor neuron ciliary neurotrophic factor receptor alpha together maintain adult motor neuron axons in vivo

作者：Lee Nancy; Serbinski Carolyn R; Braunlin Makayla R; Rasch Matthew S; Rydyznski Carolyn E; MacLennan A John^*

来源：European Journal of Neuroscience, 2016, 44(12): 3023-3034.

DOI：10.1111/ejn.13393

• axon terminals
• CNTF receptor alpha
• FluoroGold
• mouse

The molecular mechanisms maintaining adult motor innervation are comparatively unexplored relative to those involved during development. In addition to the fundamental neuroscience question, this area has important clinical ramifications given that loss of neuromuscular contact is thought to underlie several adult onset human neuromuscular diseases including amyotrophic lateral sclerosis. Indirect evidence suggests that ciliary neurotrophic factor (CNTF) receptors may contribute to adult motor neuron axon maintenance. To directly address this in vivo, we used adult onset mouse genetic disruption techniques to deplete motor neuron and muscle CNTF receptor alpha (CNTFR alpha), the essential ligand binding subunit of the receptor, and incorporated reporters labelling affected motor neuron axons and terminals. The combined depletion of motor neuron and muscle CNTFR alpha produced a large loss of motor neuron terminals and retrograde labelling of motor neurons with FluoroGold indicated axon die-back well beyond muscle, together revealing an essential role for CNTFR alpha in adult motor axon maintenance. In contrast, selective depletion of motor neuron CNTFR alpha did not affect motor innervation. These data, along with our previous work indicating no effect of muscle specific CNTFR alpha depletion on motor innervation, suggest that motor neuron and muscle CNTFR alpha function in concert to maintain motor neuron axons. The data also raise the possibility of motor neuron and/or muscle CNTFR alpha as therapeutic targets for adult neuromuscular denervating diseases.

• 出版日期2016-12