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Wnt3a promotes β‐catenin signaling and myotube formation during myogenic differentiation
Author(s) -
Langen Ramon,
Velden Jos,
Kelders Marco,
Laeremans Hilde,
Schols Annemie
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.754.21
Subject(s) - wnt3a , wnt signaling pathway , c2c12 , myocyte , skeletal muscle , microbiology and biotechnology , gsk3b , gsk 3 , signal transduction , beta catenin , glycogen synthase , chemistry , fusion gene , myogenic regulatory factors , biology , myogenesis , endocrinology , phosphorylation , gene , biochemistry , myogenin
Satellite cells are muscle precursor cells required for postnatal skeletal muscle growth and regeneration. Glycogen Synthase Kinase 3beta (GSK‐3beta) has been implicated in negative regulation of skeletal muscle growth and muscle differentiation. Two distinct cellular pools of GSK‐3beta are selectively inhibited by IGF‐I/Akt‐or canonical Wnt signaling, respectively. Since canonical Wnt signaling and subsequent stabilization of beta‐catenin is involved in embryonic muscle formation, the effects of Wnt3a on differentiating myoblasts were investigated, and compared to those resulting from GSK‐3beta inactivation by LiCl or IGF‐I. Wnt3a promoted C2C12 myoblast fusion, and induced beta‐catenin signaling in a time and dose dependent fashion. In addition, beta‐catenin‐dependent transcriptional activation was also induced after GSK‐3beta inhibition using LiCl, but not by IGF‐I. Furthermore, stimulation of muscle gene expression was only observed in response to LiCl but not Wnt3a, which uncouples the promoting effects of Wnt3a on myoblast fusion from muscle specific gene expression. These data suggest that myoblast fusion and muscle specific gene expression are controlled by distinct cellular pools of GSK‐3beta, and provide evidence for a role of GSK‐3beta as a central regulator of muscle differentiation. This work was supported by a research grant of the Netherlands Astma Foundation (NAF 3.2.02.63).