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Publication : WNT/β-Catenin Signaling Regulates Multiple Steps of Myogenesis by Regulating Step-Specific Targets.

First Author  Suzuki A Year  2015
Journal  Mol Cell Biol Volume  35
Issue  10 Pages  1763-76
PubMed ID  25755281 Mgi Jnum  J:224413
Mgi Id  MGI:5662180 Doi  10.1128/MCB.01180-14
Citation  Suzuki A, et al. (2015) WNT/beta-Catenin Signaling Regulates Multiple Steps of Myogenesis by Regulating Step-Specific Targets. Mol Cell Biol 35(10):1763-76
abstractText  Molecules involved in WNT/beta-catenin signaling show specific spatiotemporal expression and play vital roles in myogenesis; however, it is still largely unknown how WNT/beta-catenin signaling regulates each step of myogenesis. Here, we show that WNT/beta-catenin signaling can control diverse biological processes of myogenesis by regulating step-specific molecules. In order to identify the temporally specific roles of WNT/beta-catenin signaling molecules in muscle development and homeostasis, we used in vitro culture systems for both primary mouse myoblasts and C2C12 cells, which can differentiate into myofibers. We found that a blockade of WNT/beta-catenin signaling in the proliferating cells decreases proliferation activity, but does not induce cell death, through the regulation of genes cyclin A2 (Ccna2) and cell division cycle 25C (Cdc25c). During muscle differentiation, the inhibition of WNT/beta-catenin signaling blocks myoblast fusion through the inhibition of the Fermitin family homolog 2 (Fermt2) gene. Blocking WNT/beta-catenin signaling in the well-differentiated myofibers results in the failure of maintenance of their structure by disruption of cadherin/beta-catenin/actin complex formation, which plays a crucial role in connecting a myofiber's cytoskeleton to the surrounding extracellular matrix. Thus, our results indicate that WNT/beta-catenin signaling can regulate multiple steps of myogenesis, including cell proliferation, myoblast fusion, and homeostasis, by targeting step-specific molecules.
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