Beta-catenin regulates myogenesis by relieving I-mfa-mediated suppression of myogenic regulatory factors in P19 cells.
Wnt/beta-catenin signaling plays a critical role in embryonic myogenesis. Here we show that, in P19 embryonic carcinoma stem cells, Wnt/beta-catenin signaling initiates the myogenic process depends on beta-catenin-mediated relief of I-mfa (inhibitor of MyoD Family a) suppression of myogenic regulatory factors (MRFs). We found that beta-catenin interacted with I-mfa and that the interaction was enhanced by Wnt3a. In addition, we found that the interaction between beta-catenin and I-mfa was able to attenuate the interaction of I-mfa with MRFs, relieve I-mfa-mediated suppression of the transcriptional activity and cytosolic sequestration of MRFs, and initiate myogenesis in a P19 myogenic model system that expresses exogenous myogenin. This work reveals a mechanism for the regulation of MRFs during myogenesis by elucidating a beta-catenin-mediated, but lymphoid enhancing factor-1/T cell factor independent, mechanism in regulation of myogenic fate specification and differentiation of P19 mouse stem cells.
Pan
Weijun
W
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Jia
Yingying
Y
Wang
Jiyong
J
Tao
Donglei
D
Gan
Xiaoqing
X
Tsiokas
Leonidas
L
Jing
Naihe
N
Wu
Dianqing
D
Li
Lin
L
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002458:Cell Fractionation; D045744:Cell Line, Tumor; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D024510:Muscle Development / Q000502:physiology*; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology; D020798:Two-Hybrid System Techniques; D051176:beta Catenin / Q000378:metabolism*
C491077:Mdfi protein, mouse; D018006:Myogenic Regulatory Factors; D034741:RNA, Small Interfering; D051176:beta Catenin