Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/16209

TitleFGF signaling pathway in the developing chick lung : expression and inhibition studies
Author(s)Moura, Rute S.
Borges, José P. Coutinho
Pacheco, A. P.
Mota, Paulo O. da
Pinto, Jorge Correia
KeywordsFGF
FGFR
Sprouty
Llung
Chick
Issue date11-Mar-2011
PublisherPLOS
JournalPLoS ONE
Abstract(s)Fibroblast growth factors (FGF) are essential key players during embryonic development. Through their specific cognate receptors (FGFR) they activate intracellular cascades, finely regulated by modulators such as Sprouty. Several FGF ligands (FGF1, 2, 7, 9, 10 and 18) signaling through the four known FGFRs, have been implicated in lung morphogenesis. Although much is known about mammalian lung, so far, the avian model has not been explored for lung studies. Methodology/Principal Findings In this study we provide the first description of fgf10, fgfr1-4 and spry2 expression patterns in early stages of chick lung development by in situ hybridization and observe that they are expressed similarly to their mammalian counterparts. Furthermore, aiming to determine a role for FGF signaling in chick lung development, in vitro FGFR inhibition studies were performed. Lung explants treated with an FGF receptor antagonist (SU5402) presented an impairment of secondary branch formation after 48h of culture; moreover, abnormal lung growth with a cystic appearance of secondary bronchi and reduction of the mesenchymal tissue was observed. Branching and morphometric analysis of lung explants confirmed that FGFR inhibition impaired branching morphogenesis and induced a significant reduction of the mesenchyme. Conclusions/Significance This work demonstrates that FGFRs are essential for the epithelial-mesenchymal interactions that determine epithelial branching and mesenchymal growth and validate the avian embryo as a good model for pulmonary studies, namely to explore the FGF pathway as a therapeutic target.
TypeArticle
URIhttp://hdl.handle.net/1822/16209
DOI10.1371/journal.pone.0017660
ISSN1932-6203
Publisher versionhttp://www.plosone.org/
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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