Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung


  • W. Shu
  • S. Guttentag
  • Z. Wang
  • T. Andl
  • P. Ballard
  • M.M. Lu
  • S. Piccolo
  • W. Birchmeier
  • J.A. Whitsett
  • S.E. Millar
  • E.E. Morrisey


  • Developmental Biology


  • Dev Biol 283 (1): 226-239


  • Branching morphogenesis in the lung serves as a model for the complex patterning that is reiterated in multiple organs throughout development. {beta}-catenin and Wnt signaling mediate critical functions in cell fate specification and differentiation, but specific functions during branching morphogenesis have remained unclear. Here, we show that Wnt/{beta}-catenin signaling regulates proximal-distal differentiation of airway epithelium. Inhibition of Wnt/{beta}-catenin signaling, either by expression of Dkk1 or by tissue-specific deletion of β-catenin, results in disruption of distal airway development and expansion of proximal airways. Wnt/{beta}-catenin functions upstream of BMP4, FGF signaling, and N-myc. Moreover, we show that {beta}-catenin and LEF/TCF activate the promoters of BMP4 and N-myc. Thus, Wnt/{beta}-catenin signaling is a critical upstream regulator of proximal-distal patterning in the lung, in part, through regulation of N-myc, BMP4, and FGF signaling.