Semaphorin3A Signaling Is Dispensable for Motor Axon Reinnervation of the Adult Neuromuscular Junction

ENeuro
Jennifer L Shadrach, Brian A Pierchala

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 high...Continue Reading

Citations

Sep 26, 2020·Journal of Cellular and Molecular Medicine·Xin WangTianyi Wang
Jul 3, 2021·International Journal of Molecular Sciences·Greta Limoni

❮ Previous
Next ❯

Methods Mentioned

BETA
dissecting
immunoprecipitation
dissection
PCR
force measurements

Software Mentioned

LabVIEW
LAS
Prism
GraphPad
Primer3

Related Concepts

Related Feeds

Axon Guidance

Axon guidance is a complex neural developmental field that investigates mechanisms through which neurons send out axons to reach its target. Here is the latest research in this domain.