Muscle and motor neuron ciliary neurotrophic factor receptor α together maintain adult motor neuron axons in vivo.
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 α (CNTFRα), 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 CNTFRα 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 CNTFRα in adult motor axon maintenance. In contrast, selective depletion of motor neuron CNTFRα did not affect motor innervation. These data, along with our previous work indicating no effect of muscle specific CNTFRα depletion on motor innervation, suggest that motor neuron and muscle CNTFRα function in concert to maintain motor neuron axons. The data also raise the possibility of motor neuron and/or muscle CNTFRα as therapeutic targets for adult neuromuscular denervating diseases.
Department of Molecular & Cellular Physiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267-0576, USA.
Nancy
N
Lee
Department of Molecular & Cellular Physiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267-0576, USA.
Carolyn R
CR
Serbinski
Department of Molecular & Cellular Physiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267-0576, USA.
Makayla R
MR
Braunlin
Department of Molecular & Cellular Physiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267-0576, USA.
Matthew S
MS
Rasch
Department of Molecular & Cellular Physiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267-0576, USA.
Carolyn E
CE
Rydyznski
Department of Molecular & Cellular Physiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267-0576, USA.
A John
AJ
MacLennan
D000818:Animals; D001369:Axons / Q000502:physiology*; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit / Q000235:genetics / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000294:innervation*; D056347:Neuroanatomical Tract-Tracing Techniques
D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit
CNTF receptor α; FluoroGold; axon terminals; mouse