­Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system

Abstract

BackgroundFibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in the development and function of multiple organs and organ systems, including the central nervous system (CNS). FGF signaling via FGFR1, one of the three FGFRs expressed in the CNS, stimulates proliferation of stem cells during prenatal and postnatal neurogenesis and participates in regulating cell-type ratios in many developing regions of the brain. Anomalies in FGFR1 signaling have been implicated in certain neuropsychiatric disorders.Fgfr1expression has been shown, viain situhybridization, to vary spatially and temporally throughout embryonic and postnatal development of the brain. However,in situhybridization lacks sufficient resolution to identify which cell-types directly participate in FGF signaling. Furthermore, because antibodies raised against FGFR1 commonly cross-react with other members of the FGFR family, immunocytochemistry is not alone sufficient to accurately documentFgfr1expression. Here, we elucidate the identity ofFgfr1expressing cells in both the embryonic and perinatal mouse brain.MethodsTo do this, we utilized atgFGFR1-EGFPGP338GsatBAC line (tgFgfr1-EGFP+) obtained from the GENSAT project. ThetgFgfr1-EGFP+line expresses EGFP under the control of a Fgfr1 promoter, thereby causing cells endogenously expressingFgfr1to also present a positive GFP signal. Through simple immunostaining using GFP antibodies and cell-type specific antibodies, we were able to accurately determine the cell-type ofFgfr1expressing cells.ResultsThis technique revealedFgfr1expression in proliferative zones containing BLBP+ radial glial stem cells, such as the cortical and hippocampal ventricular zones, and cerebellar anlage of E14.5 mice, in addition to DCX+ neuroblasts. Furthermore, our data revealFgfr1expression in proliferative zones containing BLBP+ cells of the anterior midline, hippocampus, cortex, hypothalamus, and cerebellum of P0.5 mice, in addition to the early-formed GFAP+ astrocytes of the anterior midline.DiscussionUnderstanding when during development and whereFgfr1is expressed is critical to improving our understanding of its function during neurodevelopment as well as in the mature CNS. This information may one day provide an avenue of discovery towards understanding the involvement of aberrant FGF signaling in neuropsychiatric disorders.