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Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration

Otto, A; Schmidt, C; Luke, G; Allen, S; Valasek, P; Muntoni, F; Lawrence-Watt, D; (2008) Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration. J CELL SCI , 121 (17) 2939 - 2950. 10.1242/jcs.026534.

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Abstract

Satellite cells represent the stem cell population of adult skeletal muscle. The molecular mechanisms that control the proliferation of satellite cells are not well understood. In this study, we show that in response to injury, myofibres activate Wnt ligand transcription and activate a reporter cell line that is sensitive to the canonical Wnt-signalling pathway. Activated satellite cells on isolated cultured myofibres show robust expression of activated-beta-catenin (Act-beta-Cat), a key downstream transcriptional coactivator of canonical Wnt signalling. We provide evidence that the Wnt family of secreted glycoproteins act on satellite cells in a ligand-specific manner. Overexpression of Wnt1, Wnt3a or Wnt5a protein causes a dramatic increase in satellite-cell proliferation. By contrast, exposure of satellite cells to Wnt4 or Wnt6 diminishes this process. Moreover, we show that the prolonged satellite-cell quiescence induced by inhibitory Wnt is reversible and exposing inhibited satellite cells to stimulatory Wnt signalling restores their proliferation rate. Stimulatory Wnt proteins induce premature satellite cell BrdU incorporation as well as nuclear translocation of Act-beta-Cat. Finally, we provide evidence that the Act-beta-Cat translocation observed in single fibres during in vitro culture also occurs in cases of acute and chronic skeletal muscle regeneration in rodents and humans. We propose that Wnt proteins may be key factors that regulate the rate of satellite- cell proliferation on adult muscle fibres during the wound- healing response.

Type: Article
Title: Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration
DOI: 10.1242/jcs.026534
Keywords: satellite cell, Wnt signalling, beta-catenin, skeletal muscle, regeneration, BETA-CATENIN, PARAXIAL MESODERM, SELF-RENEWAL, CYCLIN D1, EXPRESSION, MYOGENESIS, ACTIVATION, MECHANISM, PATHWAY, FIBERS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
URI: http://discovery.ucl.ac.uk/id/eprint/111884
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