title: Wnt/β-catenin signaling via Axin2 is required for myogenesis and, together with YAP/Taz and Tead1, active in IIa/IIx muscle fibers.
abstract: Canonical Wnt/β-catenin signaling plays an important role in myogenic differentiation, but its physiological role in muscle fibers remains elusive. Here, we studied activation of Wnt/β-catenin signaling in adult muscle fibers and muscle stem cells in an Axin2 reporter mouse. Axin2 is a negative regulator and a target of Wnt/β-catenin signaling. In adult muscle fibers, Wnt/β-catenin signaling is only detectable in a subset of fast fibers that have a significantly smaller diameter than other fast fibers. In the same fibers, immunofluorescence staining for YAP/Taz and Tead1 was detected. Wnt/β-catenin signaling was absent in quiescent and activated satellite cells. Upon injury, Wnt/β-catenin signaling was detected in muscle fibers with centrally located nuclei. During differentiation of myoblasts expression of Axin2, but not of Axin1, increased together with Tead1 target gene expression. Furthermore, absence of Axin1 and Axin2 interfered with myoblast proliferation and myotube formation, respectively. Treatment with the canonical Wnt3a ligand also inhibited myotube formation. Wnt3a activated TOPflash and Tead1 reporter activity, whereas neither reporter was activated in the presence of Dkk1, an inhibitor of canonical Wnt signaling. We propose that Axin2-dependent Wnt/β-catenin signaling is involved in myotube formation and, together with YAP/Taz/Tead1, associated with reduced muscle fiber diameter of a subset of fast fibers.
authors: Institute of Biochemistry, Fahrstrasse 17, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen D-91054, Germany.
authors: Danyil
authors: D
authors: Huraskin
authors: Institute of Biochemistry, Fahrstrasse 17, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen D-91054, Germany.
authors: Nane
authors: N
authors: Eiber
authors: Nikolaus-Fiebiger-Center of Molecular Medicine, Glückstrasse 6, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen D-91054, Germany.
authors: Martin
authors: M
authors: Reichel
authors: Leibniz Institute for Age Research/Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, Jena D-07745, Germany.
authors: Laura M
authors: LM
authors: Zidek
authors: Institute of Biochemistry, Fahrstrasse 17, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen D-91054, Germany.
authors: Bojana
authors: B
authors: Kravic
authors: Nikolaus-Fiebiger-Center of Molecular Medicine, Glückstrasse 6, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen D-91054, Germany.
authors: Dominic
authors: D
authors: Bernkopf
authors: Leibniz Institute for Age Research/Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, Jena D-07745, Germany.
authors: Julia
authors: J
authors: von Maltzahn
authors: Nikolaus-Fiebiger-Center of Molecular Medicine, Glückstrasse 6, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen D-91054, Germany.
authors: Jürgen
authors: J
authors: Behrens
authors: Institute of Biochemistry, Fahrstrasse 17, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen D-91054, Germany said.hashemolhosseini@fau.de.
authors: Said
authors: 0000-0002-6564-5649
authors: S
authors: Hashemolhosseini
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C111729:Axin2 protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C083215:Tead1 protein, mouse; D014157:Transcription Factors; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D051176:beta Catenin; D000217:Acyltransferases; C486363:tafazzin protein, mouse
keywords: Axin2; Muscle fibers; Satellite cells; Skeletal muscle; Tead1; Wwtr1; Yap1