Terminal Schwann cells participate in neuromuscular synapse remodeling during reinnervation following nerve injury.
Schwann cells (SCs) at neuromuscular junctions (NMJs) play active roles in synaptic homeostasis and repair. We have studied how SCs contribute to reinnervation of NMJs using vital imaging of mice whose motor axons and SCs are transgenically labeled with different colors of fluorescent proteins. Motor axons most commonly regenerate to the original synaptic site by following SC-filled endoneurial tubes. During the period of denervation, SCs at the NMJ extend elaborate processes from the junction, as shown previously, but they also retract some processes from territory they previously occupied within the endplate. The degree of this retraction depends on the length of the period of denervation. We show that the topology of the remaining SC processes influences the branching pattern of regenerating axon terminals and the redistribution of acetylcholine receptors (AChRs). Upon arriving at the junction, regenerating axons follow existing SC processes within the old synaptic site. Some of the AChR loss that follows denervation is correlated with failure of portions of the old synaptic site that lack SC coverage to be reinnervated. New AChR clustering is also induced by axon terminals that follow SC processes extended during denervation. These observations show that SCs participate actively in the remodeling of neuromuscular synapses following nerve injury by their guidance of axonal reinnervation.
Section of Molecular Cell and Developmental Biology, The University of Texas at Austin, Texas 78712, Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, and Department of Biology, Texas A&M University, College Station, Texas 77843.
Hyuno
H
Kang
Le
L
Tian
Michelle
M
Mikesh
Jeff W
JW
Lichtman
Wesley J
WJ
Thompson
D000818:Animals; D003714:Denervation; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D059348:Peripheral Nerve Injuries / Q000473:pathology* / Q000503:physiopathology*; D011950:Receptors, Cholinergic / Q000378:metabolism; D020127:Recovery of Function; D012583:Schwann Cells / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors
D008164:Luminescent Proteins; D011950:Receptors, Cholinergic
glial cell; nerve injury; neuromuscular junction; regeneration; synaptic plasticity; synaptic structure