title: FGFR2 is required for airway basal cell self-renewal and terminal differentiation.
abstract: Airway stem cells slowly self-renew and produce differentiated progeny to maintain homeostasis throughout the lifespan of an individual. Mutations in the molecular regulators of these processes may drive cancer or degenerative disease, but are also potential therapeutic targets. Conditionally deleting one copy of FGF receptor 2 (FGFR2) in adult mouse airway basal cells results in self-renewal and differentiation phenotypes. We show that FGFR2 signalling correlates with maintenance of expression of a key transcription factor for basal cell self-renewal and differentiation: SOX2. This heterozygous phenotype illustrates that subtle changes in receptor tyrosine kinase signalling can have significant effects, perhaps providing an explanation for the numerous changes seen in cancer.
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK.
authors.forename: Gayan I
authors.identifier: 0000-0002-0916-6686
authors.initials: GI
authors.lastname: Balasooriya
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK.
authors.forename: Maja
authors.initials: M
authors.lastname: Goschorska
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK.|School of Cellular and Molecular Medicine, Faculty of Biomedical Sciences, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, BS8 1TD, UK.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Piddini
authors.affiliation: Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK e.rawlins@gurdon.cam.ac.uk.|Wellcome Trust/MRC Stem Cell Institute and Department of Pathology, University of Cambridge, Cambridge, CB2 1QN, UK.
authors.forename: Emma L
authors.identifier: 0000-0001-7426-3792
authors.initials: EL
authors.lastname: Rawlins
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D000066673:Cell Self Renewal; D003114:Colony-Forming Units Assay; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D057895:Haploinsufficiency; D006579:Heterozygote; D006706:Homeostasis; D008168:Lung / Q000166:cytology*; D008810:Mice, Inbred C57BL; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D014132:Trachea / Q000166:cytology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D055748:SOXB1 Transcription Factors; D005346:Fibroblast Growth Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2; D001616:beta-Galactosidase
keywords: Cre-Lox; Lung; Mouse; Progenitor; Trachea