title: Prolonged FGF signaling is necessary for lung and liver induction in Xenopus.
abstract: BACKGROUND
  FGF signaling plays numerous roles during organogenesis of the embryonic gut tube. Mouse explant studies suggest that different thresholds of FGF signaling from the cardiogenic mesoderm induce lung, liver, and pancreas lineages from the ventral foregut progenitor cells. The mechanisms that regulate FGF dose in vivo are unknown. Here we use Xenopus embryos to examine the hypothesis that a prolonged duration of FGF signaling from the mesoderm is required to induce foregut organs.
  
  
  RESULTS
  We show that both mesoderm and FGF signaling are required for liver and lung development in Xenopus; formally demonstrating that this important step in organ induction is conserved with other vertebrate species. Prolonged contact with the mesoderm and persistent FGF signaling through both MEK and PI3K over an extended period of time are required for liver and lung specification. Inhibition of FGF signaling results in reduced liver and lung development, with a modest expansion of the pancreas/duodenum progenitor domain. Hyper-activation of FGF signaling has the opposite effect expanding liver and lung gene expression and repressing pancreatic markers. We show that FGF signaling is cell autonomously required in the endoderm and that a dominant negative FGF receptor decreases the ability of ventral foregut progenitor cells to contribute to the lung and liver buds.
  
  
  CONCLUSIONS
  These results suggest that the liver and lungs are specified at progressively later times in development requiring mesoderm contact for different lengths of time. Our data suggest that this is achieved at least in part through prolonged FGF signaling. In addition to providing a foundation for further mechanistic studies on foregut organogenesis using the experimental advantages of the Xenopus system, these data have implications for the directed differentiation of stem cells into foregut lineages.
authors.affiliation: Perinatal Institute, Divisions of Developmental Biology, University of Cincinnati, Cincinnati, OH 45229, USA.
authors.forename: Emily T
authors.initials: ET
authors.lastname: Shifley
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kenny
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rankin
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Zorn
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004707:Endoderm / Q000196:embryology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D017403:In Situ Hybridization; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D038081:Organogenesis; D010179:Pancreas / Q000196:embryology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D046509:Tissue Culture Techniques; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: D029867:Xenopus Proteins; D005346:Fibroblast Growth Factors; D019869:Phosphatidylinositol 3-Kinases