TY  - JOUR
AU  - Meier, Florian
AU  - Giesert, Florian
AU  - Delic, Sabit
AU  - Faus-Kessler, Theresa
AU  - Matheus, Friederike
AU  - Simeone, Antonio
AU  - Hölter, Sabine M
AU  - Kühn, Ralf
AU  - Vogt-Weisenhorn, Daniela
AU  - Wurst, Wolfgang
AU  - Prakash, Nilima
TI  - FGF/FGFR2 signaling regulates the generation and correct positioning of Bergmann glia cells in the developing mouse cerebellum.
JO  - PLOS ONE
VL  - 9
IS  - 7
SN  - 1932-6203
CY  - San Francisco, California, US
PB  - PLOS
M1  - DZNE-2020-03800
SP  - e101124
PY  - 2014
AB  - 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.
KW  - Animals
KW  - Cell Survival
KW  - Cerebellum: cytology
KW  - Cerebellum: embryology
KW  - Cerebellum: metabolism
KW  - Fibroblast Growth Factors: metabolism
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Neuroglia: cytology
KW  - Neuroglia: metabolism
KW  - Receptor, Fibroblast Growth Factor, Type 2: genetics
KW  - Receptor, Fibroblast Growth Factor, Type 2: metabolism
KW  - Signal Transduction
KW  - Fibroblast Growth Factors (NLM Chemicals)
KW  - Fgfr2 protein, mouse (NLM Chemicals)
KW  - Receptor, Fibroblast Growth Factor, Type 2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24983448
C2  - pmc:PMC4077754
DO  - DOI:10.1371/journal.pone.0101124
UR  - https://pub.dzne.de/record/137478
ER  -