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pubmed-article:15907834pubmed:abstractTextBranching 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 beta-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.lld:pubmed
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pubmed-article:15907834pubmed:articleTitleWnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung.lld:pubmed
pubmed-article:15907834pubmed:affiliationDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.lld:pubmed
pubmed-article:15907834pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:15907834pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:15907834pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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