Abstract
Background. Wnt signaling is involved in muscle formation through β-catenin-dependent or -independent pathways, but interactions with other signaling pathways including transforming growth factor β/Smad have not been precisely elucidated. Results. As Wnt4 stimulates myogenic differentiation by antagonizing myostatin (GDF8) activity, we examined the role of Wnt4 signaling during muscle differentiation in the C2C12 myoblast cell line. Among several extrinsic signaling molecules examined in a microarray analysis of C2C12 cells during the transition from cell proliferation to differentiation after mitogen deprivation, bone morphogenetic protein 4 (BMP4) expression was prominently increased. Wnt4 overexpression had similar effects on BMP4 expression. BMP4 was able to inhibit muscle differentiation when added to the culture medium. BMP4 and noggin had no effects on the cellular localization of β-catenin induced by Wnt3a; however, the BMP4-induced phosphorylation of Smad1/5/8 was enhanced by Wnt4, but not by Wnt3a. The BMP antagonist noggin effectively stimulated muscle differentiation through binding to endogenous BMPs, and the effect of noggin was enhanced by the presence of Wnt3a and Wnt4. Conclusion. These results suggest that BMP/Smad pathways are modified through Wnt signaling during the transition from progenitor cell proliferation to myogenic differentiation, although Wnt/β-catenin signaling is not modified with BMP/Smad signaling.
Highlights
Wnt signaling is involved in muscle formation through β-catenin-dependent or -independent pathways, but interactions with other signaling pathways including transforming growth factor β/Smad have not been precisely elucidated
At an initial step of axial determination, bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) superfamily, and Wnt family members have been recognized as key mediators involved in the formation of the dorsal/ventral axis and the anterior/posterior axis, in addition to the fibroblast growth factor family and the hedgehog family [5, 6]
We examined possible interactions between Wnt4 and bone morphogenetic protein 4 (BMP4) with respect to myogenic differentiation and found that BMP4/Smad signaling was affected by Wnt signaling during differentiation of myogenic progenitor cells
Summary
Wnt signaling is involved in muscle formation through β-catenin-dependent or -independent pathways, but interactions with other signaling pathways including transforming growth factor β/Smad have not been precisely elucidated. These results suggest that BMP/Smad pathways are modified through Wnt signaling during the transition from progenitor cell proliferation to myogenic differentiation, Wnt/β-catenin signaling is not modified with BMP/Smad signaling. The formation of skeletal muscle from paraxial mesoderm is influenced by signals from the neural tube and the dorsal ectoderm, including Wnt and BMP4, and by the determination of myogenic cell fate by intrinsic factors including MyoD and Myf5 [7, 8]. Satellite cells proliferate and differentiate during myotube turnover through signaling by Wnt family members [9, 10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
