Impaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice.

Brain Research
Karen Müller SmithFlora M Vaccarino

Abstract

Fibroblast growth factor receptor (FGFR) signaling determines the size of the cerebral cortex by regulating the amplification of radial glial stem cells, and participates in the formation of midline glial structures. We show that Fgfr1 and Fgfr2 double knockouts (FGFR DKO) generated by Cre-mediated recombination driven by the human GFAP promoter (hGFAP) have reduced cerebellar size due to reduced proliferation of radial glia and other glial precursors in late embryonic and neonatal FGFR DKO mice. The proliferation of granule cell progenitors (GCPs) in the EGL was also reduced, leading to reduced granule cell numbers. Furthermore, both inward migration of granule cells into the inner granule cell layer (IGL) and outward migration of GABA interneurons into the molecular layer (ML) were arrested, disrupting layer and lobular morphology. Purkinje neurons and their dendrites, which were not targeted by Cre-mediated recombination of Fgf receptors, were also misplaced in FGFR DKO mice, possibly as a consequence of altered Bergmann glia orientation or reduced granule cell number. Our findings indicate a dual role for FGFR signaling in cerebellar morphogenesis. The first role is to amplify the number of granule neuron precursors in the ...Continue Reading

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Citations

Jan 19, 2013·Molecular Neurobiology·Haiwei XuXiaotang Fan
Aug 29, 2013·Progress in Neurobiology·Annalisa Buffo, Ferdinando Rossi
Aug 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Daisuke KoyabuMarcelo R Sánchez-Villagra
Jan 23, 2016·Frontiers in Molecular Neuroscience·Francesca Pischedda, Giovanni Piccoli
Apr 25, 2015·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Robert Lalonde, Catherine Strazielle
Sep 3, 2016·Acta Neuropathologica Communications·Paola CaporaliMaria Teresa Fiorenza
Apr 23, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Oné R Pagán
Aug 24, 2021·Frontiers in Aging Neuroscience·Jian-Wei ZhuRu-Xiang Xu

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