Journal Article

DZNE-2020-03800

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png FGF/FGFR2 signaling regulates the generation and correct positioning of Bergmann glia cells in the developing mouse cerebellum.

Meier, F. ; Giesert, F. ; Delic, S. ; Faus-Kessler, T. ; Matheus, F. ; Simeone, A. ; Hölter, S. M. ; Kühn, R. ; Vogt-Weisenhorn, D.DZNE* ; Wurst, W. (Corresponding author) ; Prakash, N.

2014
PLOS San Francisco, California, US

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Please use a persistent id in citations: doi:10.1371/journal.pone.0101124

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.

Keyword(s): Animals (MeSH) ; Cell Survival (MeSH) ; Cerebellum: cytology (MeSH) ; Cerebellum: embryology (MeSH) ; Cerebellum: metabolism (MeSH) ; Fibroblast Growth Factors: metabolism (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Neuroglia: cytology (MeSH) ; Neuroglia: metabolism (MeSH) ; Receptor, Fibroblast Growth Factor, Type 2: genetics (MeSH) ; Receptor, Fibroblast Growth Factor, Type 2: metabolism (MeSH) ; Signal Transduction (MeSH) ; Fibroblast Growth Factors ; Fgfr2 protein, mouse ; Receptor, Fibroblast Growth Factor, Type 2

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Contributing Institute(s):

1. Ext HZM (Ext HZM)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2014

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Database coverage:
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