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PMID: 17170140 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Developmental stage-specific biphasic roles of Wnt/beta-catenin signaling in cardiomyogenesis and hematopoiesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 52 ·2006-12-26 ·Pages 19812-7

Naito AT, Shiojima I, Akazawa H, Hidaka K, Morisaki T, Kikuchi A, Komuro I

Abstract

Although Wingless (Wg)/Wnt signaling has been implicated in heart development of multiple organisms, conflicting results have been reported regarding the role of Wnt/beta-catenin pathway in cardiac myogenesis: Wg/armadillo signaling promotes heart development in Drosophila, whereas activation of Wnt/beta-catenin signaling inhibits heart formation in avians and amphibians. Using an in vitro system of mouse ES cell differentiation into cardiomyocytes, we show here that Wnt/beta-catenin signaling exhibits developmental stage-specific, biphasic, and antagonistic effects on cardiomyogenesis and hematopoiesis/vasculogenesis. Activation of the Wnt/beta-catenin pathway in the early phase during embryoid body (EB) formation enhances ES cell differentiation into cardiomyocytes while suppressing the differentiation into hematopoietic and vascular cell lineages. In contrast, activation of Wnt/beta-catenin signaling in the late phase after EB formation inhibits cardiomyocyte differentiation and enhances the expression of hematopoietic/vascular marker genes through suppression of bone morphogenetic protein signaling. Thus, Wnt/beta-catenin signaling exhibits biphasic and antagonistic effects on cardiomyogenesis and hematopoiesis/vasculogenesis, depending on the stage of development.

MeSH Terms
Animals Bone Morphogenetic Proteins/genetics Cell Differentiation Cells, Cultured Embryonic Stem Cells/cytology,metabolism Gene Expression Regulation, Developmental Hematopoiesis Humans Mice Myocytes, Cardiac/cytology,metabolism Signal Transduction Time Factors Wnt Proteins/genetics,metabolism beta Catenin/metabolism
Chemicals
Bone Morphogenetic Proteins Wnt Proteins beta Catenin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Naito Atsuhiko T
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Shiojima Ichiro
Akazawa Hiroshi
Hidaka Kyoko
Morisaki Takayuki
Kikuchi Akira
Komuro Issei
References (30)
30 references, click to expand
  1. Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development.
    Genes Dev. 1999 Dec 1;13(23):3149-59 PMID: 10601040
  2. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.
    Nat Genet. 2000 Apr;24(4):372-6 PMID: 10742100
  3. BMP signaling is required for heart formation in vertebrates.
    Dev Biol. 2000 Aug 15;224(2):226-37 PMID: 10926762
  4. Wnt signals from the neural tube block ectopic cardiogenesis.
    Genes Dev. 2001 Feb 1;15(3):255-60 PMID: 11159906
  5. Wnt antagonism initiates cardiogenesis in Xenopus laevis.
    Genes Dev. 2001 Feb 1;15(3):304-15 PMID: 11159911
  6. Inhibition of Wnt activity induces heart formation from posterior mesoderm.
    Genes Dev. 2001 Feb 1;15(3):316-27 PMID: 11159912
  7. Heads or tails: Wnts and anterior-posterior patterning.
    Curr Biol. 2001 Sep 4;11(17):R713-24 PMID: 11553348
  8. Chamber-specific differentiation of Nkx2.5-positive cardiac precursor cells from murine embryonic stem cells.
    FASEB J. 2003 Apr;17(6):740-2 PMID: 12594186
  9. A Wnt- and beta -catenin-dependent pathway for mammalian cardiac myogenesis.
    Proc Natl Acad Sci U S A. 2003 May 13;100(10):5834-9 PMID: 12719544
  10. A transcriptional response to Wnt protein in human embryonic carcinoma cells.
    BMC Dev Biol. 2002 Jul 2;2:8 PMID: 12095419
  11. Early stage-specific inhibitions of cardiomyocyte differentiation and expression of Csx/Nkx-2.5 and GATA-4 by phosphatidylinositol 3-kinase inhibitor LY294002.
    Exp Cell Res. 2003 Nov 15;291(1):56-69 PMID: 14597408
  12. Wnt-3a and Dvl induce neurite retraction by activating Rho-associated kinase.
    Mol Cell Biol. 2004 May;24(10):4487-501 PMID: 15121866
  13. The Wnt signaling pathway in development and disease.
    Annu Rev Cell Dev Biol. 2004;20:781-810 PMID: 15473860
  14. Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo.
    Nature. 1995 Mar 30;374(6521):464-7 PMID: 7700357
  15. Heart development in Drosophila requires the segment polarity gene wingless.
    Dev Biol. 1995 Jun;169(2):619-28 PMID: 7781903
  16. The wingless signaling pathway is directly involved in Drosophila heart development.
    Dev Biol. 1996 Jul 10;177(1):104-16 PMID: 8660881
  17. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development.
    Development. 1996 Oct;122(10):2977-86 PMID: 8898212
  18. A role for bone morphogenetic proteins in the induction of cardiac myogenesis.
    Genes Dev. 1997 Feb 15;11(4):451-62 PMID: 9042859
  19. Bone morphogenetic proteins induce cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase TAK1 and cardiac transcription factors Csx/Nkx-2.5 and GATA-4.
    Mol Cell Biol. 1999 Oct;19(10):7096-105 PMID: 10490646
  20. Haemangioblast commitment is initiated in the primitive streak of the mouse embryo.
    Nature. 2004 Dec 2;432(7017):625-30 PMID: 15577911
  21. Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins.
    J Biol Chem. 2005 Jan 28;280(4):2498-502 PMID: 15545262
  22. Wnt signalling in stem cells and cancer.
    Nature. 2005 Apr 14;434(7035):843-50 PMID: 15829953
  23. Embryonic stem cell differentiation: emergence of a new era in biology and medicine.
    Genes Dev. 2005 May 15;19(10):1129-55 PMID: 15905405
  24. Phosphatidylinositol 3-kinase-Akt pathway plays a critical role in early cardiomyogenesis by regulating canonical Wnt signaling.
    Circ Res. 2005 Jul 22;97(2):144-51 PMID: 15994435
  25. Deletion of the selection cassette, but not cis-acting elements, in targeted Flk1-lacZ allele reveals Flk1 expression in multipotent mesodermal progenitors.
    Blood. 2006 Jan 1;107(1):111-7 PMID: 16166582
  26. Mesoderm induction: from caps to chips.
    Nat Rev Genet. 2006 May;7(5):360-72 PMID: 16619051
  27. BMP signaling restricts hemato-vascular development from lateral mesoderm during somitogenesis.
    Development. 2006 Jun;133(11):2177-87 PMID: 16672337
  28. Canonical Wnt signaling is required for development of embryonic stem cell-derived mesoderm.
    Development. 2006 Oct;133(19):3787-96 PMID: 16943279
  29. Hematopoietic stem cell and multilineage defects generated by constitutive beta-catenin activation.
    Nat Immunol. 2006 Oct;7(10):1037-47 PMID: 16951686
  30. Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block.
    Nat Immunol. 2006 Oct;7(10):1048-56 PMID: 16951689
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0605768103
Published
2006-12-26
Epub
2006-00-14
Pages
19812-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1750922
Subset
IM
Corrections
CommentIn
PMID: 17537915
External Links
PubMed source DOI: 10.1073/pnas.0605768103 PMC Full Text View journal details
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