期刊
DEVELOPMENTAL BIOLOGY
卷 319, 期 2, 页码 426-436出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2008.04.009
关键词
fibroblast growth factor 9 (FGF9); fibroblast growth factor receptor (FGFR); WNT2a; WNT7b; beta-Catenin; lung development; mesenchyme
资金
- NHLBI NIH HHS [T32 HL007275-27, T32 HL07873, T32 HL007873, T32 HL007275] Funding Source: Medline
- NIDDK NIH HHS [P30 DK052574, P30 DK052574-059001] Funding Source: Medline
Lung mesenchyme is a critical determinant of the shape and size of the lung, the extent and patterning of epithelial branching, and the formation of the pulmonary vasculature and interstitial mesenchymal components of the adult lung. Fibroblast growth factor 9 (FGF9) is a critical regulator of lung mesenchymal growth; however, upstream mechanisms that modulate the FGF mesenchymal signal and the downstream targets of mesenchymal FGF signaling are poorly understood. Here we have identified a robust regulatory network in which mesenchymal FGF signaling regulates beta-Catenin mediated WNT signaling in lung mesenchyme. By conditionally inactivating beta-Catenin in lung mesenchyme, we show that mesenchymal WNT-beta-Catenin signaling is essential for lung development and acts to regulate the cell cycle G1 to S transition and the FGF responsiveness of mesenchyme. Together, both FGF and WNT signaling pathways function to sustain mesenchymal growth and coordinate epithelial morphogenesis during the pseudoglandular stage of lung development. (c) 2008 Elsevier Inc. All rights reserved.
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