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Publication : Mesothelial- and epithelial-derived FGF9 have distinct functions in the regulation of lung development.

First Author  Yin Y Year  2011
Journal  Development Volume  138
Issue  15 Pages  3169-77
PubMed ID  21750028 Mgi Jnum  J:175543
Mgi Id  MGI:5286005 Doi  10.1242/dev.065110
Citation  Yin Y, et al. (2011) Mesothelial- and epithelial-derived FGF9 have distinct functions in the regulation of lung development. Development 138(15):3169-77
abstractText  Fibroblast growth factor (FGF) 9 is a secreted signaling molecule that is expressed in lung mesothelium and epithelium and is required for lung development. Embryos lacking FGF9 show mesenchymal hypoplasia, decreased epithelial branching and, by the end of gestation, hypoplastic lungs that cannot support life. Mesenchymal FGF signaling interacts with beta-catenin-mediated WNT signaling in a feed-forward loop that functions to sustain mesenchymal FGF responsiveness and mesenchymal WNT/beta-catenin signaling. During pseudoglandular stages of lung development, Wnt2a and Wnt7b are the canonical WNT ligands that activate mesenchymal WNT/beta-catenin signaling, whereas FGF9 is the only known ligand that signals to mesenchymal FGF receptors (FGFRs). Here, we demonstrate that mesothelial- and epithelial-derived FGF9, mesenchymal Wnt2a and epithelial Wnt7b have unique functions in lung development in mouse. Mesothelial FGF9 and mesenchymal WNT2A are principally responsible for maintaining mesenchymal FGF-WNT/beta-catenin signaling, whereas epithelial FGF9 primarily affects epithelial branching. We show that FGF signaling is primarily responsible for regulating mesenchymal proliferation, whereas beta-catenin signaling is a required permissive factor for mesenchymal FGF signaling.
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