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2016 ; 36
(38
): 9770-81
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Schwann Cells in Neuromuscular Junction Formation and Maintenance
#MMPMID27656017
Barik A
; Li L
; Sathyamurthy A
; Xiong WC
; Mei L
J Neurosci
2016[Sep]; 36
(38
): 9770-81
PMID27656017
show ga
The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor
nerve terminals, postjunctional muscle membranes, and terminal Schwann cells
(TSCs) that cover the nerve-muscle contact. NMJ formation requires intimate
communications among the three different components. Unlike nerve-muscle
interaction, which has been well characterized, less is known about the role of
SCs in NMJ formation and maintenance. We show that SCs in mice lead nerve
terminals to prepatterned AChRs. Ablating SCs at E8.5 (i.e., prior nerve arrival
at the clusters) had little effect on aneural AChR clusters at E13.5, suggesting
that SCs may not be necessary for aneural clusters. SC ablation at E12.5, a time
when phrenic nerves approach muscle fibers, resulted in smaller and fewer
nerve-induced AChR clusters; however, SC ablation at E15.5 reduced AChR cluster
size but had no effect on cluster density, suggesting that SCs are involved in
AChR cluster maturation. Miniature endplate potential amplitude, but not
frequency, was reduced when SCs were ablated at E15.5, suggesting that
postsynaptic alterations may occur ahead of presynaptic deficits. Finally,
ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and
neuromuscular transmission deficits. Miniature endplate potential amplitude was
reduced 3 d after SC ablation, but both amplitude and frequency were reduced 6 d
after. Together, these results indicate that SCs are not only required for NMJ
formation, but also necessary for its maintenance; and postsynaptic function and
structure appeared to be more sensitive to SC ablation. SIGNIFICANCE STATEMENT:
Neuromuscular junctions (NMJs) are critical for survival and daily functioning.
Defects in NMJ formation during development or maintenance in adulthood result in
debilitating neuromuscular disorders. The role of Schwann cells (SCs) in NMJ
formation and maintenance was not well understood. We genetically ablated SCs
during development and after NMJ formation to investigate the consequences of the
ablation. This study reveals a critical role of SCs in NMJ formation as well as
maintenance.
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