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PMID:19686689

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Citation

Goss, AM, Tian, Y, Tsukiyama, T, Cohen, ED, Zhou, D, Lu, MM, Yamaguchi, TP and Morrisey, EE (2009) Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut. Dev. Cell 17:290-8

Abstract

Patterning of the primitive foregut promotes appropriate organ specification along its anterior-posterior axis. However, the molecular pathways specifying foregut endoderm progenitors are poorly understood. We show here that Wnt2/2b signaling is required to specify lung endoderm progenitors within the anterior foregut. Embryos lacking Wnt2/2b expression exhibit complete lung agenesis and do not express Nkx2.1, the earliest marker of the lung endoderm. In contrast, other foregut endoderm-derived organs, including the thyroid, liver, and pancreas, are correctly specified. The phenotype observed is recapitulated by an endoderm-restricted deletion of beta-catenin, demonstrating that Wnt2/2b signaling through the canonical Wnt pathway is required to specify lung endoderm progenitors within the foregut. Moreover, activation of canonical Wnt/beta-catenin signaling results in the reprogramming of esophagus and stomach endoderm to a lung endoderm progenitor fate. Together, these data reveal that canonical Wnt2/2b signaling is required for the specification of lung endoderm progenitors in the developing foregut.

Links

PubMed PMC2763331 Online version:10.1016/j.devcel.2009.06.005

Keywords

Animals; Body Patterning/physiology; Digestive System/anatomy & histology; Digestive System/embryology; Endoderm/cytology; Endoderm/physiology; Lung/anatomy & histology; Lung/embryology; Mice; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction/physiology; Stem Cells/cytology; Stem Cells/physiology; Wnt Proteins/genetics; Wnt Proteins/metabolism; Wnt2 Protein/genetics; Wnt2 Protein/metabolism; beta Catenin/genetics; beta Catenin/metabolism

Significance

Annotations

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

MOUSE:WNT2B

acts_upstream_of_or_within

GO:0060492: lung induction

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98954

P

Seeded From UniProt

complete

MOUSE:WNT2B

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98954

P

  • occurs_in:(EMAPA:16548)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060492: lung induction

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1261834

P

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1261834

P

  • occurs_in:(EMAPA:16548)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0060492: lung induction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2148567

P

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1261834
MGI:MGI:98954

P

  • occurs_in:(EMAPA:16548)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1261834

P

occurs_in:(EMAPA:16548)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060492: lung induction

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1261834

P

has_participant:(EMAPA:16548)

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0060501: positive regulation of epithelial cell proliferation involved in lung morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

Seeded From UniProt

complete

MOUSE:WNT2

acts_upstream_of_or_within

GO:0002053: positive regulation of mesenchymal cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4361155

P

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0060070: canonical Wnt signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1261834
MGI:MGI:98954

P

occurs_in:(EMAPA:16548)

Seeded From UniProt

complete

MOUSE:CTNB1

acts_upstream_of_or_within

GO:0060492: lung induction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2148567

P

has_participant:(EMAPA:16548)

Seeded From UniProt

complete


See also

References

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