Activation of the Wnt/β-catenin signaling cascade after traumatic nerve injury

S. Kurimoto, J. Jung, M. Tapadia, J. Lengfeld, D. Agalliu, M. Waterman, T. Mozaffar, R. Gupta

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Recent data have shown that preservation of the neuromuscular junction (NMJ) after traumatic nerve injury helps to improve functional recovery with surgical repair via matrix metalloproteinase-3 (MMP3) blockade. As such, we sought to explore additional pathways that may augment this response. Wnt3a has been shown to inhibit acetylcholine receptor (AChR) clustering via β-catenin-dependent signaling in the development of the NMJ. Therefore, we hypothesized that Wnt3a and β-catenin are associated with NMJ destabilization following traumatic denervation. A critical size nerve defect was created by excising a 10-mm segment of the sciatic nerve in mice. Denervated muscles were then harvested at multiple time points for immunofluorescence staining, quantitative real-time PCR, and western blot analysis for Wnt3a and β-catenin levels. Moreover, a novel Wnt/β-catenin transgenic reporter mouse line was utilized to support our hypothesis of Wnt activation after traumatic nerve injury. The expression of Wnt3a mRNA was significantly increased by 2. weeks post-injury and remained upregulated for 2. months. Additionally, β-catenin was activated at 2. months post-injury relative to controls. Correspondingly, immunohistochemical analysis of denervated transgenic mouse line TCF/Lef:H2B-GFP muscles demonstrated that the number of GFP-positive cells was increased at the motor endplate band. These collective data support that post-synaptic AChRs destabilize after denervation by a process that involves the Wnt/β-catenin pathway. As such, this pathway serves as a potential therapeutic target to prevent the motor endplate degeneration that occurs following traumatic nerve injury.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
StatePublished - May 1 2015

Bibliographical note

Funding Information:
This work was supported by NIH NINDS 2RO1NS049203-06A1 .

Publisher Copyright:
© 2015 IBRO.


  • Neuromuscular junction
  • Peripheral nerve
  • Traumatic nerve injury
  • Wnt signaling


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