Shinichiro Nishimatsu    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Natural Sciences,    Position   Professor
Language	English
Title	Wnt signaling during transition from cell proliferation to differentiation in myoblast cells.
Conference	WNT2011
Conference Type	International society and overseas society
Presentation Type	Poster notice
Lecture Type	General
Publisher and common publisher	◎Tanaka Shingo, Nishimatsu Shin-ichiro, Yamamura Masahiro, Nohno Tsutomu
Date	2011/07/01
Venue (city and name of the country)	LA, USA
Society abstract	WNT2011 Abstract Book 25
Summary	Wnt3a and beta-catenin are required to induce transcription of muscle-specific genes in embryonic carcinoma cells, also cause satellite-cell proliferation during adult skeletal muscle regeneration. beta-Catenin forms a complex with TCF/Lef-1, and eventually induces expression of the cyclin D1 and c-myc genes, although expression of these genes is suppressed during differentiation of the myoblast cells. Using C2C12 cells, we examined the transcriptional change in signaling components in Wnt pathways during myoblast proliferation and differentiation. We found that Wnt9a, Sfrp2 and porcupine expressions are significantly elevated in the differentiating C2C12 cells. Overexpression of Wnt3a induced less troponin T-positive myotubes than that of Wnt4 and Wnt5a. Wnt3a-induced TOFFLASH activity was reduced by co-expression with Wnt4, suggesting that Wnt3a promotes the myoblast proliferation whereas Wnt4 stimulates the differentiation. C2C12 cell proliferation and motility were also reduced by Wnt4 expression. A small-molecule inhibitor of beta-catenin/Tcf complex formation, FH535, reduced basal beta- catenin protein and decreased the cell proliferation. K252a, a protein kinase inhibitor, increased membrane-bound beta-catenin and enhanced the myoblast fusion. These results suggest that different Wnt ligands control subcellular localization of beta-catenin and manage the myoblast proliferation and myotube formation. beta-Catenin is acting as a molecular switch regulating the transition from cell proliferation to myogenic differentiation.