DOI: 10.1073/pnas.0935626100. A Wnt- and β-catenin-dependent pathway for mammalian cardiac myogenesis

A Wnt- and β-catenin-dependent pathway for mammalian cardiac myogenesis

10.1073/pnas.0935626100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Acquisition of a cardiac fate by embryonic mesodermal cells is a fundamental step in heart formation. Heart development in frogs and avians requires positive signals from adjacent endoderm, including bone morphogenic proteins, and is antagonized by a second secreted signal, Wnt proteins, from neural tube. By contrast, mechanisms of mesodermal commitment to create heart muscle in mammals are largely unknown. In addition, Wnt-dependent signals can involve either a canonical β-catenin pathway or other, alternative mediators. Here, we tested the involvement of Wnts and β-catenin in mammalian cardiac myogenesis by using a pluripotent mouse cell line (P19CL6) that recapitulates early steps for cardiac specification. In this system, early and late cardiac genes are up-regulated by 1% DMSO, and spontaneous beating occurs. Notably, Wnt3A and Wnt8A were induced days before even the earliest cardiogenic transcription factors. DMSO induced biochemical mediators of Wnt signaling (decreased phosphorylation and increased levels of β-catenin), which were suppressed by Frizzled-8/Fc, a soluble Wnt antagonist. DMSO provoked T cell factor-dependent transcriptional activity; thus, induction of Wnt proteins by DMSO was functionally coupled. Frizzled-8/Fc inhibited the induction of cardiogenic transcription factors, cardiogenic growth factors, and sarcomeric myosin heavy chains. Likewise, differentiation was blocked by constitutively active glycogen synthase kinase 3β, an intracellular inhibitor of the Wnt/β-catenin pathway. Conversely, lithium chloride, which inhibits glycogen synthase kinase 3β, and Wnt3A-conditioned medium up-regulated early cardiac markers and the proportion of differentiated cells. Thus, Wnt/β-catenin signaling is activated at the inception of mammalian cardiac myogenesis and is indispensable for cardiac differentiation, at least in this pluripotent model system.

Bibliography

Nakamura, T., Sano, M., Songyang, Z., & Schneider, M. D. (2003). A Wnt- and Î²-catenin-dependent pathway for mammalian cardiac myogenesis. Proceedings of the National Academy of Sciences, 100(10), 5834â5839.

Authors 4

Teruya Nakamura (first)
Motoaki Sano (additional)
Zhou Songyang (additional)
Michael D. Schneider (additional)

References 46 Referenced 222

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Dates

Type	When
Created	22 years, 3 months ago (May 13, 2003, 2:28 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 6:37 p.m.)
Indexed	1 month, 3 weeks ago (July 1, 2025, 9:48 a.m.)
Issued	22 years, 3 months ago (April 28, 2003)
Published	22 years, 3 months ago (April 28, 2003)
Published Online	22 years, 3 months ago (April 28, 2003)
Published Print	22 years, 3 months ago (May 13, 2003)

Funders 0

None

BibTeX

@article{Nakamura_2003, title={A Wnt- and β-catenin-dependent pathway for mammalian cardiac myogenesis}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0935626100}, DOI={10.1073/pnas.0935626100}, number={10}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Nakamura, Teruya and Sano, Motoaki and Songyang, Zhou and Schneider, Michael D.}, year={2003}, month=apr, pages={5834–5839} }

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