title: FGF signaling pathway in the developing chick lung: expression and inhibition studies.
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. Although much is known about mammalian lung, so far, the avian model has not been explored for lung studies.
  
  
  RESULTS
  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 48 h 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
  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.
authors.affiliation: School of Health Sciences, Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal. rutemoura@ecsaude.uminho.pt
authors.forename: Rute S
authors.initials: RS
authors.lastname: Moura
authors.forename: José P
authors.initials: JP
authors.lastname: Coutinho-Borges
authors.forename: Ana P
authors.initials: AP
authors.lastname: Pacheco
authors.forename: Paulo O
authors.initials: PO
authors.lastname: Damota
authors.forename: Jorge
authors.initials: J
authors.lastname: Correia-Pinto
mesh_terms: D000818:Animals; D002642:Chick Embryo; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D051526:Fibroblast Growth Factor 10; D008565:Membrane Proteins; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D004121:Dimethyl Sulfoxide