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PMID:17360443

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Citation

Liu, Y, Asakura, M, Inoue, H, Nakamura, T, Sano, M, Niu, Z, Chen, M, Schwartz, RJ and Schneider, MD (2007) Sox17 is essential for the specification of cardiac mesoderm in embryonic stem cells. Proc. Natl. Acad. Sci. U.S.A. 104:3859-64

Abstract

Early steps for cardiac specification are problematic for the study of mammalian embryos, which has favored using pluripotent cells that recapitulate cardiac myogenesis. Furthermore, circuits governing cardiac specification have relevance to the application of ES cells and other cells for heart repair. In mouse teratocarcinoma cells, canonical Wnts that inhibit heart formation in avian or amphibian embryos and explants activate cardiogenesis, paradoxically. Here, we show that the Wnt/beta-catenin pathway also is essential for cardiac myogenesis to occur in ES cells, acting at a gastrulation-like stage, mediating mesoderm formation and patterning (two prerequisites for cardiac myogenesis itself). Among genes associated temporally with this step was Sox17, encoding an endodermal HMG-box transcription factor. Using lentiviral vectors for RNA interference in differentiating ES cells, an essential role for Sox17 was proven in cardiac muscle cell formation. Sox17 short-hairpin RNA suppresses cardiac myogenesis selectively, acting subsequent to mesoderm formation yet before induction of Mesp1 and Mesp2, a pair of related basic helix-loop-helix transcription factors that together are indispensable for creating heart mesoderm. Sox17 short-hairpin RNA blocks cardiac myogenesis non-cell autonomously and impairs the induction of Hex, a homeodomain transcription factor that is known to be required for the production of endoderm-derived heart-inducing factors.

Links

PubMed PMC1820674 Online version:10.1073/pnas.0609100104

Keywords

Animals; Body Patterning; Cell Differentiation; Embryonic Stem Cells/cytology; Gene Expression Regulation; HMGB Proteins/physiology; Lentivirus/metabolism; Mesoderm/cytology; Mesoderm/metabolism; Mice; Myocardium/cytology; Oligonucleotide Array Sequence Analysis; Protein Structure, Tertiary; RNA Interference; SOXF Transcription Factors; Signal Transduction; Transcription Factors/metabolism; Transcription Factors/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DKK1

involved_in

GO:0090090: negative regulation of canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NOGG

involved_in

GO:0030514: negative regulation of BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX17

involved_in

GO:0003308: negative regulation of Wnt signaling pathway involved in heart development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX17

involved_in

GO:2000043: regulation of cardiac cell fate specification

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GATA4

acts_upstream_of_or_within

GO:0030509: BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0002322)

Seeded From UniProt

complete

MOUSE:GATA4

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

occurs_in:(CL:0002322)

Seeded From UniProt

complete

MOUSE:WNT3A

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0002322)
  • has_regulation_target:(MGI:MGI:107543)

Seeded From UniProt

complete

MOUSE:FZD8

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0002322)
  • has_regulation_target:(MGI:MGI:107543)

Seeded From UniProt

complete

MOUSE:FZD8

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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