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PMID:20159597

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Citation

Tian, Y, Yuan, L, Goss, AM, Wang, T, Yang, J, Lepore, JJ, Zhou, D, Schwartz, RJ, Patel, V, Cohen, ED and Morrisey, EE (2010) Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development. Dev. Cell 18:275-87

Abstract

Little is understood about the molecular mechanisms underlying the morphogenesis of the posterior pole of the heart. Here we show that Wnt2 is expressed specifically in the developing inflow tract mesoderm, which generates portions of the atria and atrio-ventricular canal. Loss of Wnt2 results in defective development of the posterior pole of the heart, resulting in a phenotype resembling the human congenital heart syndrome complete common atrio-ventricular canal. The number and proliferation of posterior second heart field progenitors is reduced in Wnt2(-/-) mutants. Moreover, these defects can be rescued in a temporally restricted manner through pharmacological inhibition of Gsk-3beta. We also show that Wnt2 works in a feedforward transcriptional loop with Gata6 to regulate posterior cardiac development. These data reveal a molecular pathway regulating the posterior cardiac mesoderm and demonstrate that cardiovascular defects caused by loss of Wnt signaling can be rescued pharmacologically in vivo.

Links

PubMed PMC2846539 Online version:10.1016/j.devcel.2010.01.008

Keywords

Animals; Disease Models, Animal; Enzyme Inhibitors/pharmacology; Female; Fetal Heart/drug effects; Fetal Heart/embryology; Fetal Heart/physiology; GATA6 Transcription Factor/genetics; GATA6 Transcription Factor/physiology; Gene Expression Regulation, Developmental/drug effects; Glycogen Synthase Kinase 3/antagonists & inhibitors; Heart Defects, Congenital/embryology; Heart Defects, Congenital/genetics; Heart Defects, Congenital/physiopathology; Humans; Lithium Chloride/pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Models, Cardiovascular; Phenotype; Pregnancy; Signal Transduction; Wnt2 Protein/deficiency; Wnt2 Protein/genetics; Wnt2 Protein/physiology

Significance

Annotations

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

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060317: cardiac epithelial to mesenchymal transition

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

  • occurs_in:(EMAPA:16546)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

  • occurs_in:(EMAPA:16546)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060045: positive regulation of cardiac muscle cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

  • regulates_o_occurs_in:(EMAPA:17320)|regulates_o_occurs_in:(EMAPA:17326)

Seeded From UniProt

complete

MOUSE:WNT2

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

  • has_input:(MGI:MGI:107516)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0055009: atrial cardiac muscle tissue morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

Seeded From UniProt

complete

MOUSE:CTNB1

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(EMAPA:16105)
  • has_input:(MGI:MGI:107516)

Seeded From UniProt

complete

MOUSE:CTNB1

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

  • has_input:(MGI:MGI:107516)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060317: cardiac epithelial to mesenchymal transition

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

occurs_in:(EMAPA:16546)

Seeded From UniProt

complete

MOUSE:WNT2

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

has_regulation_target:(MGI:MGI:107516)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0055009: atrial cardiac muscle tissue morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

has_participant:(EMAPA:17320)|has_participant:(EMAPA:17326)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060045: positive regulation of cardiac muscle cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

regulates_o_occurs_in:(EMAPA:17320)|regulates_o_occurs_in:(EMAPA:17326)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

occurs_in:(EMAPA:16546)

Seeded From UniProt

complete

MOUSE:CTNB1

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

has_regulation_target:(MGI:MGI:107516)

Seeded From UniProt

complete

MOUSE:CTNB1

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(EMAPA:16105)
  • has_participant:(MGI:MGI:107516)

Seeded From UniProt

complete


See also

References

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