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Originally published In Press as doi:10.1074/jbc.M112141200 on February 20, 2002

J. Biol. Chem., Vol. 277, Issue 18, 15393-15399, May 3, 2002
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beta -Catenin Is Essential and Sufficient for Skeletal Myogenesis in P19 Cells*

Helen PetropoulosDagger and Ilona S. Skerjanc§

From the Department of Biochemistry, Medical Sciences Building, University of Western Ontario, London, Ontario N6A 5C1, Canada

Wnt1 and Wnt3a are signaling factors known to play a role in the induction of myogenesis in the myotome of the differentiating somite. Both factors may transduce their signal by a conserved pathway that leads to transcriptional regulation by beta -catenin/Lef1. beta -Catenin and Lef1 are found in the myotome prior to MyoD expression. We have utilized the P19 cell system to study the mechanisms by which Wnt3a may activate MyoD expression and subsequent skeletal muscle development. We have isolated P19 cell lines that stably express either Wnt3a or activated beta -catenin and found that aggregation of these cells results in the induction of myogenesis compared with control cells. Pax3, Gli2, Mox1, and Six1 were expressed during Wnt3a and beta -catenin-induced differentiation prior to MyoD expression. Furthermore, we have shown that the nuclear function of beta -catenin was essential for skeletal myogenesis in P19 cells by overexpression of a dominant negative beta -catenin/engrailed chimera. Primitive streak factors were present, but expression of Pax3, Mox1, Gli2, and Six1 was lost in these cells, indicating that nuclear beta -catenin is essential for specification of mesodermal precursors to the myogenic lineage. Therefore, Wnt signaling, acting via beta -catenin, is necessary and sufficient for skeletal myogenesis in P19 cells.

* This work was supported in part by the Neuromuscular Research Partnership, an initiative of ALS Canada, Muscular Dystrophy Association of Canada, and Canadian Institutes of Health Research.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Supported by a Natural Sciences and Engineering Research Council of Canada postgraduate studentship and an Ontario graduate scholarship.

§ To whom correspondence should be addressed. Tel.: 519-661-2111 (ext. 86867); Fax: 519-661-3175; E-mail: skerjanc@uwo.ca.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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