title: An inducible system for the study of FGF signalling in early amphibian development.
abstract: The use of a novel inducible FGF signalling system in the frog Xenopus laevis is reported. We show that the lipophilic, synthetic, dimerizing agent AP20187 is able to rapidly activate signalling through an ectopically expressed mutant form of FGFR1 (iFGFR1) in Xenopus embryos. iFGFR1 lacks an extracellular ligand binding domain and contains an AP20187 binding domain fused to the intracellular domain of mouse FGFR1. Induction of signalling by AP20187 is possible until at least early neurula stages, and we demonstrate that ectopically expressed iFGFR1 protein persists until late neurula stages. We show that activation of signalling through iFGFR1 can mimic a number of previously reported FGF activities, including mesoderm induction, repression of anterior development, and neural posteriorization. We show that competence to morphological posteriorization of the anteroposterior axis by FGF signalling only extends until about stage 10.5. We demonstrate that the competence of neural tissue to express the posterior markers Hoxa7 and Xcad3, in response to FGF signalling, is lost by the end of gastrula stages. We also show that activation of FGF signalling stimulates morphogenetic movements in neural tissue until at least the end of the gastrula stage.
authors.affiliation: Department of Biology, PO Box 373, University of York, YO10 5YW, York, United Kingdom.
authors.forename: M E
authors.initials: ME
authors.lastname: Pownall
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Welm
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Freeman
authors.forename: David M
authors.initials: DM
authors.lastname: Spencer
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Rosen
authors.forename: Harry V
authors.initials: HV
authors.lastname: Isaacs
mesh_terms: D000818:Animals; D036703:Blastula / Q000378:metabolism; D019521:Body Patterning; D019281:Dimerization; D005326:Fetal Proteins / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D005775:Gastrula / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009420:Nervous System / Q000196:embryology; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology*
chemical_list: C463061:AP20187; C096851:Cdx4 protein, Xenopus; D005326:Fetal Proteins; D018398:Homeodomain Proteins; C492048:Hoxa7 protein, Xenopus; C492047:Hoxa7 protein, mouse; D009363:Neoplasm Proteins; D017468:Receptors, Fibroblast Growth Factor; D029867:Xenopus Proteins; D005346:Fibroblast Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D016559:Tacrolimus