Schwann cell processes guide axons reinnervating the neuromuscular junction

Terminal Schwann cells, one of three components of the neuromuscular junction, play an active role in synaptic homeostasis and repair. Terminal Schwann cells and their processes cover precisely the axon terminal branches and underlying postsynaptic acetylcholine receptors in normal junctions. Upon muscle denervation, these terminal Schwann cells extend elaborate processes beyond the boundary of the junction but retract their processes within the old synaptic site. After nerve injury, regenerating axons grow following old Schwann cell tubes and reinnervate the old synaptic sites.; My study using time-lapse in vivo imaging with transgenic mice expressing green fluorescent protein (GFP) and cyan green fluorescent protein (CFP) in their Schwann cells and motor neurons, respectively, shows that the topology of the Schwann cell processes formed following denervation influences the branching pattern of regenerating axon terminals and the redistribution of postsynaptic receptors. In early reinnervation, regenerating axons follow existing Schwann cell processes rather than underlying AChRs. A great portion of loss of receptor sites after denervation is caused by failure of reinnervation in some area of the old synaptic sites where abandoned by Schwann cells while denervated. New AChR clustering is also caused by axon terminals that grow following Schwann cell processes.; Taken together, these results suggest that Schwann cells play an important role in the repair and remodeling of the neuromuscular synapse by inducing and guiding axonal reinnervation.