Abstract:
:The development of the heart is essential for embryogenesis and precedes development of other organs. However, the mechanisms involved in embryonic cardiac development are ill-defined. Recent evidence suggests that Smad and Wnt signaling pathways are important in stem cell fate determination and their commitment to cardiovascular differentiation. We have previously reported that bone morphogenetic proteins (BMP)-2, -5, and -7 and fibroblast growth factors (FGF)-2 and -4 secreted from the adjoining endodermal cells favor cardiac differentiation in murine embryonic stem (ES) cells. Here, we demonstrate that BMP-2, -5, and -7 stimulate receptor-activated Smad1, 5, and 8, which in turn causes oligomerization of Smad4 in the nucleus. We further delineate the role of Wnt signaling pathway as evidenced by induction of Wnt3 and Wnt8b, stimulation of FRP-1, inhibition of GSK-B, accumulation of cytosolic beta-catenin, and transcription of target genes, including c-myc and cyclin-D1. We also ascertained the specificity of BMP- and Wnt-evoked activation of signaling cascades. Our data are consistent with the hypothesis that BMP-dependent activation of transcription factors including GATA-4, Nkx2.5, and MEF-2C augments cardiac differentiation mediated by cooperative control of Smad and Wnt signaling pathways. Our results provide a solid foundation for further study of the biochemistry of cardiac differentiation from stem cells.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Pal R,Khanna Adoi
10.1089/scd.2006.15.29keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
29-39issue
1eissn
1547-3287issn
1557-8534journal_volume
15pub_type
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