RRC ID 53168
Author Shadrach JL, Pierchala BA.
Title Semaphorin3A Signaling Is Dispensable for Motor Axon Reinnervation of the Adult Neuromuscular Junction.
Journal eNeuro
Abstract The neuromuscular junction (NMJ) is a specialized synapse that is formed by motor axon innervation of skeletal muscle fibers. The maintenance of motor-muscle connectivity is critical for the preservation of muscle tone and generation of movement. Injury can induce a robust regenerative response in motor axons, but severe trauma or chronic denervation resulting from neurodegenerative disease typically leads to inefficient repair and poor functional recovery. The axon guidance molecule Semaphorin3A (Sema3A) has been implicated as a negative regulator of motor innervation. Upon binding to a plexinA-neuropilin1 (Npn1) receptor complex, Sema3A initiates a downstream signaling cascade that results in axonal repulsion. Here, we established a reproducible nerve crush model to quantify motor nerve regeneration. We then used that model to investigate the role of Sema3A signaling at the adult NMJ. In contrast to previous findings, we found that Sema3A and Npn1 mRNA decrease in response to denervation, suggesting that Sema3A-Npn1 signaling may regulate NMJ reinnervation. To directly test that hypothesis, we used inducible knockout models to ubiquitously delete Sema3A or Npn1 from adult mice. Despite demonstrating that we could achieve highly efficient gene deletion, disruption of Sema3A-Npn1 signaling did not affect the normal maintenance of the NMJ or disrupt motor axon reinnervation after a denervating injury.
Volume 5(3)
Published 2018-1-1
DOI 10.1523/ENEURO.0155-17.2018
PII eN-NRS-0155-17
PMID 29774231
PMC PMC5955010
MeSH Animals Axons / metabolism* Gene Expression Mice, Inbred C57BL Mice, Transgenic Motor Neurons / metabolism* Muscle, Skeletal / metabolism Myelin Sheath / metabolism Nerve Crush / methods Nerve Regeneration* Neuromuscular Junction / metabolism* Neuropilin-1 / physiology Peroneal Nerve / injuries* Peroneal Nerve / physiopathology Semaphorin-3A / metabolism* Signal Transduction Spinal Cord / metabolism
IF 3.544
Times Cited 0
Mice RBRC01106