Abstract
Schwann cells (SCs) are integral to the formation and function of the peripheral nervous system (PNS). Exemplifying their importance, the loss or dysfunction of SCs is a feature of a myriad of diseases and conditions that compromise the PNS. Thus, it remains essential to understand the rules that govern the proliferation, differentiation and reconnection of Schwann cells with peripheral axons. Here, we examined the consequences of locally and acutely ablating terminal Schwann cells (tSCs) at the adult mouse neuromuscular junction (NMJ) by using mice expressing diphtheria toxin receptor (DTR) preferentially in tSCs compared to myelinating SCs followed by local application of diphtheria toxin (DTX). After DTX application, tSCs died but, importantly and contrary to expectations, their associated motor axons did not fully degenerate. Within 3 weeks, tSCs returned and reestablished coverage of the synapse with increased numbers. Furthermore, the post-synaptic muscle fibers displayed increased distinct clusters of acetylcholine receptors and axon terminals exhibited numerous terminal varicosities. The lack of degeneration of bare motor axon terminals and the morphological remodeling that occurs upon the return of tSCs to the NMJ may have wider implications for the mechanisms governing tSC occupancy of the adult NMJ and for conditions that adversely affect tSCs.
Highlights
Schwann cells (SCs) are integral to the formation and function of the peripheral nervous system (PNS)
This is consistent with a previous report, which showed that diphtheria toxin receptor (DTR) expression in myelinating SCs was limited to the paranodal microvilli, and that diphtheria toxin (DTX) injection did not affect sciatic nerve compound action potentials, suggesting a limited susceptibility of myelinating SCs to DTX ablation[34]
These results, taken together with our observations that myelinating SCs tended to remain after terminal Schwann cells (tSCs) were ablated, suggest that the expression of DTR was more robust in tSCs compared to myelinating SCs, which may have led to a greater susceptibility of tSCs to the acute DTX application
Summary
Schwann cells (SCs) are integral to the formation and function of the peripheral nervous system (PNS). We examined the consequences of locally and acutely ablating terminal Schwann cells (tSCs) at the adult mouse neuromuscular junction (NMJ) by using mice expressing diphtheria toxin receptor (DTR) preferentially in tSCs compared to myelinating SCs followed by local application of diphtheria toxin (DTX). The lack of degeneration of bare motor axon terminals and the morphological remodeling that occurs upon the return of tSCs to the NMJ may have wider implications for the mechanisms governing tSC occupancy of the adult NMJ and for conditions that adversely affect tSCs. Schwann cells (SCs), the glia of the peripheral nervous system (PNS), serve a variety of important roles[1,2,3]. To achieve a more localized ablation, we bathed a single sternomastoid (STM) muscle in DTX diluted in lactated Ringer’s Using this method, there was widespread death of tSCs across the STM, but the mice still appeared healthy and behaved normally 3 weeks after DTX application
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