title: FGF/FGFR2 signaling regulates the generation and correct positioning of Bergmann glia cells in the developing mouse cerebellum.
abstract: The normal cellular organization and layering of the vertebrate cerebellum is established during embryonic and early postnatal development by the interplay of a complex array of genetic and signaling pathways. Disruption of these processes and of the proper layering of the cerebellum usually leads to ataxic behaviors. Here, we analyzed the relative contribution of Fibroblast growth factor receptor 2 (FGFR2)-mediated signaling to cerebellar development in conditional Fgfr2 single mutant mice. We show that during embryonic mouse development, Fgfr2 expression is higher in the anterior cerebellar primordium and excluded from the proliferative ventricular neuroepithelium. Consistent with this finding, conditional Fgfr2 single mutant mice display the most prominent defects in the anterior lobules of the adult cerebellum. In this context, FGFR2-mediated signaling is required for the proper generation of Bergmann glia cells and the correct positioning of these cells within the Purkinje cell layer, and for cell survival in the developing cerebellar primordium. Using cerebellar microexplant cultures treated with an FGFR agonist (FGF9) or antagonist (SU5402), we also show that FGF9/FGFR-mediated signaling inhibits the outward migration of radial glia and Bergmann glia precursors and cells, and might thus act as a positioning cue for these cells. Altogether, our findings reveal the specific functions of the FGFR2-mediated signaling pathway in the generation and positioning of Bergmann glia cells during cerebellar development in the mouse.
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Meier
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Giesert
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany; Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Sabit
authors.initials: S
authors.lastname: Delic
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Faus-Kessler
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Matheus
authors.affiliation: Centre of Genetics Engineering (CEINGE) Biotecnologie Avanzate, European School of Molecular Medicine and Institute of Genetics and Biophysics "A. Buzzati-Traverso", Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Simeone
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany; Technische Universität München-Weihenstephan, Lehrstuhl für Entwicklungsgenetik c/o Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kühn
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany; Technische Universität München-Weihenstephan, Lehrstuhl für Entwicklungsgenetik c/o Helmholtz Zentrum München, Neuherberg, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Standort München, München, Germany; Max-Planck Institute of Psychiatry, München, Germany.
authors.forename: Daniela M Vogt
authors.initials: DM
authors.lastname: Weisenhorn
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany; Technische Universität München-Weihenstephan, Lehrstuhl für Entwicklungsgenetik c/o Helmholtz Zentrum München, Neuherberg, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Standort München, München, Germany; Max-Planck Institute of Psychiatry, München, Germany; Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München, München, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany; Technische Universität München-Weihenstephan, Lehrstuhl für Entwicklungsgenetik c/o Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Nilima
authors.initials: N
authors.lastname: Prakash
mesh_terms: D000818:Animals; D002470:Cell Survival; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005346:Fibroblast Growth Factors; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2