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

Dev Cell. 2009 Aug;17(2):290-8. doi: 10.1016/j.devcel.2009.06.005.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Wnt Proteins
  • Wnt2 Protein
  • Wnt2b protein, mouse
  • beta Catenin