Branching morphogenesis in the lung serves as a model for the complex patterning that is reiterated in multiple organs throughout development. β-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/β-catenin signaling regulates proximal-distal differentiation of airway epithelium. Inhibition of Wnt/β-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/β-catenin functions upstream of BMP4, FGF signaling, and N-myc. Moreover, we show that β-catenin and LEF/TCF activate the promoters of BMP4 and N-myc. Thus, Wnt/β-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.
|Number of pages||14|
|State||Published - Jul 1 2005|
Bibliographical noteFunding Information:
The authors would like to thank Peter Klein for the TCF3 expression plasmids, Arnold Levine for the β-catenin/4145 expression plasmid, and Constance Scharff for SU5402. The authors thank Jonathan Epstein for helpful suggestions during these studies. These studies were supported by funding from the NIH to E.E.M. (P01 HL075215) and S.E.M. (R01 AR47709). E.E.M. is an Established Investigator of the American Heart Association.
- Lung development
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology