Molecular Neurobiology

, Volume 49, Issue 1, pp 574–589 | Cite as

Wnt Signaling in Skeletal Muscle Dynamics: Myogenesis, Neuromuscular Synapse and Fibrosis

  • Pedro Cisternas
  • Juan P. Henriquez
  • Enrique Brandan
  • Nibaldo C. InestrosaEmail author


The signaling pathways activated by Wnt ligands are related to a wide range of critical cell functions, such as cell division, migration, and synaptogenesis. Here, we summarize compelling evidence on the role of Wnt signaling on several features of skeletal muscle physiology. We briefly review the role of Wnt pathways on the formation of muscle fibers during prenatal and postnatal myogenesis, highlighting its role on the activation of stem cells of the adult muscles. We also discuss how Wnt signaling regulates the precise formation of neuromuscular synapses, by modulating the differentiation of presynaptic and postsynaptic components, particularly regarding the clustering of acetylcholine receptors on the muscle membrane. In addition, based on previous evidence showing that Wnt pathways are linked to several diseases, such as Alzheimer's and cancer, we address recent studies indicating that Wnt signaling plays a key role in skeletal muscle fibrosis, a disease characterized by an increase in the extracellular matrix components leading to failure in muscle regeneration, tissue disorganization and loss of muscle activity. In this context, we also discuss the possible cross-talk between the Wnt/β-catenin pathway with two other critical profibrotic pathways, transforming growth factor β and connective tissue growth factor, which are potent stimulators of the accumulation of connective tissue, an effect characteristic of the fibrotic condition. As it has emerged in other pathological conditions, we suggests that muscle fibrosis may be a consequence of alterations of Wnt signaling activity.


Wnt signaling Muscle development Neuromuscular junction Fibrosis 



This work was supported by grants from the Basal Center of Excellence in Aging and Regeneration (CONICYT-PFB 12/2007) and FONDECYT (no. 1120156 to N.C.I. and no. 1130321 to J.P.H.). PC was a postdoctoral fellow from the PFB (12/2007) grant to NCI and EB. Graphic work was carried out by Graphique-Science (

Conflicts of Interest

There is no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Pedro Cisternas
    • 1
  • Juan P. Henriquez
    • 2
  • Enrique Brandan
    • 1
  • Nibaldo C. Inestrosa
    • 1
    Email author
  1. 1.Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile
  2. 2.Departamento de Biología Celular, Facultad de Ciencias BiológicasUniversidad de ConcepciónConcepciónChile

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