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Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut.

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.

Pubmed ID: 19686689

Authors

  • Goss AM
  • Tian Y
  • Tsukiyama T
  • Cohen ED
  • Zhou D
  • Lu MM
  • Yamaguchi TP
  • Morrisey EE

Journal

Developmental cell

Publication Data

August 18, 2009

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL075215
  • Agency: NHLBI NIH HHS, Id: HL087825
  • Agency: NHLBI NIH HHS, Id: P01 HL075215
  • Agency: NHLBI NIH HHS, Id: P01 HL075215-020002
  • Agency: NHLBI NIH HHS, Id: P01 HL075215-03
  • Agency: NHLBI NIH HHS, Id: R01 HL087825
  • Agency: NHLBI NIH HHS, Id: R01 HL087825-02
  • Agency: NHLBI NIH HHS, Id: R01 HL087825-03
  • Agency: NHLBI NIH HHS, Id: R01 HL087825-05

Mesh Terms

  • Animals
  • Body Patterning
  • Digestive System
  • Endoderm
  • Lung
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction
  • Stem Cells
  • Wnt Proteins
  • Wnt2 Protein
  • beta Catenin