Fibroblast Growth Factor Receptor 1 Is Required for the Proliferation of Hippocampal Progenitor Cells and for Hippocampal Growth in Mouse

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Abstract
Fibroblast growth factor receptor 1 (Fgfr1) is expressed at high levels by progenitor cells of the ventricular zone (VZ) within the hippocampal primordium. To investigate the role ofFgfr1in these cells,in vivoCre recombination of “floxed” Fgfr1 alleles was directed to cells of the radial glial lineage by using the human glial fibrillary acidic protein promoter. Radial glial-like cells of the hippocampal VZ are the progenitors of pyramidal neurons and granule cells of hippocampal dentate gyrus (DG). Mice carrying nullFgfr1alleles (Fgfr1Δflox) in cells of this lineage showed a dramatic loss ofFgfr1gene expression throughout the embryonic dorsal telencephalon. TheseFgfr1Δfloxmice exhibited a ∼30% decrease in dividing radial glial progenitor cells in the hippocampal VZ and DG in the late embryonic period, progressing to a ∼50-60% loss at birth, without any changes in cell survival. In addition, no FGF2-sensitive neural stem cells could be isolated from theFgfr1Δfloxhippocampal neuroepithelium, whereas epidermal growth factor-sensitive neural stem cells were not affected. The number of hippocampal pyramidal neurons and DG granule cells was ∼30-50% decreased from the perinatal period through adulthood, and the number of parvalbumin-containing interneurons was similarly decreased in both the DG and pyramidal cell fields. We conclude thatFgfr1is necessary for hippocampal growth, because it promotes the proliferation of hippocampal progenitors and stem cells during development.