FGF Signaling Pathway in the Developing Chick Lung Expression and Inhibition Studies 英文参考文献.docVIP

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FGF Signaling Pathway in the Developing Chick Lung Expression and Inhibition Studies 英文参考文献.doc

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FGF Signaling Pathway in the Developing Chick Lung Expression and Inhibition Studies 英文参考文献

FGFSignalingPathwayintheDevelopingChickLung: ExpressionandInhibitionStudies RuteS.Moura*,Jose′ P.Coutinho-Borges,AnaP.Pacheco,PauloO.daMota,JorgeCorreia-Pinto SchoolofHealthSciences,LifeandHealthSciencesResearchInstitute(ICVS),UniversityofMinho,Braga,Portugal Abstract Background: 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.Althoughmuchisknownaboutmammalianlung,sofar,theavianmodelhasnotbeenexploredforlung studies. Methodology/Principal Findings: In this study we provide the first description of fgf10, fgfr1-4 and spry2 expression patternsinearlystagesofchicklungdevelopmentbyinsituhybridizationandobservethattheyareexpressedsimilarlyto theirmammaliancounterparts.Furthermore, aimingtodeterminearoleforFGF signalinginchicklung development, in vitroFGFRinhibitionstudieswereperformed.LungexplantstreatedwithanFGFreceptorantagonist(SU5402)presentedan impairmentofsecondarybranchformationafter48hofculture;moreover,abnormallunggrowthwithacysticappearance ofsecondarybronchiandreductionofthemesenchymaltissuewasobserved.Branchingandmorphometricanalysisoflung explants confirmed that FGFR inhibition impaired branching morphogenesis and induced a significant reduction of the mesenchyme. Conclusions/Significance:ThisworkdemonstratesthatFGFRsareessentialfortheepithelial-mesenchymalinteractionsthat determineepithelialbranchingandmesenchymalgrowthandvalidatetheavianembryoasagoodmodelforpulmonary studies,namelytoexploretheFGFpathwayasatherapeutictarget. Citation:MouraRS,Coutinho-BorgesJP,PachecoAP,daMotaPO,Correia-PintoJ(2011)FGFSignalingPathwayintheDevelopingChickLung:Expressionand InhibitionStudies.PLoSONE6(3):e17660.doi:10.1371/journal.pone.0017660 Editor:BruceRiley,TexasAM