期刊
DEVELOPMENTAL BIOLOGY
卷 283, 期 1, 页码 226-239出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2005.04.014
关键词
Wnt; beta-catenin; dickkopf-1; BMP; FGF; lung development
资金
- NHLBI NIH HHS [P01 HL075215] Funding Source: Medline
- NIAMS NIH HHS [R01 AR47709] Funding Source: Medline
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 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. (C) 2005 Elsevier Inc. All rights reserved.
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