Wnt/β-Catenin signaling acts at multiple developmental stages to promote mammalian cardiogenesis

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, United States
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 01/2009; 7(24):3815-8. DOI: 10.4161/cc.7.24.7189
Source: PubMed


Despite decades of progress in cardiovascular biology, heart disease remains the leading cause of death in the developed world. Recently, cell-based therapy has emerged as a promising avenue for future therapeutics. However, the molecular signals that regulate cardiac progenitor cells are not well-understood. Wnt/beta-catenin signaling is essential for expansion and differentiation of cardiac progenitors in mouse embryos and in the embryonic stem cell system. Studies from our laboratory and others highlight the pivotal roles of Wnt/beta-catenin signaling in the multiple steps of cardiogenesis and provide insights into understanding the complex regulation of cardiac progenitors. Here we discuss the required roles of Wnt/beta-catenin signaling at the different stages of heart development.

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    • "Wnt/beta-catenin signaling has previously been established to play a biphasic role in cardiac differentiation of EBs [44], [45], [46]. Specification of early cardiac progenitor cells is promoted, while later differentiation of progenitor cells into cardiomyocytes is repressed by Wnt/beta-catenin signaling [44], [45], [46]. Since we showed above that endogenous CS could negatively regulate the Wnt/beta-catenin pathway in EBs, we hypothesized that CS has a similar biphasic role in cardiac differentiation through its ability to regulate the Wnt/beta-catenin pathway. "
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    • "The cardiovascular system requires precisely regulated canonical Wnt/β-catenin (Wnt) signaling in order to develop properly, as Wnt signaling has been shown to both promote and restrict cardiomyocyte (CM) formation during distinct phases of development (Kwon et al., 2008; Tzahor, 2007). Understanding how Wnt signaling directs CM development is necessary for the generation of therapies capable of healing injured or malformed human hearts. "
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    • "The second or “epigenetic” relates to heritable changes in gene function that occur independently of alterations in primary DNA sequence. The best-characterized epigenetic modifications are DNA methylation and histone modifications, both of which function in Wnt signaling, a critical pathway in early cardiomyogenesis [24, 44, 45, 47, 93], neurogenesis [50, 94–96], and placentation [48]. Vertebrate DNA methylation is in general restricted to cytosine (C) nucleotides in the sequence CG, known as CpG islands. "
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