Quantitative assessment of fibroblast growth factor receptor 1 expression in neurons and glia

Abstract

BackgroundFibroblast growth factors (FGFs) and their receptors (FGFRs) have numerous functions in the developing and adult central nervous system (CNS). For example, the FGFR1 receptor is important for proliferation and fate specification of radial glial cells in the cortex and hippocampus, oligodendrocyte proliferation and regeneration, midline glia morphology and soma translocation, Bergmann glia morphology, and cerebellar morphogenesis. In addition, FGFR1 signaling in astrocytes is required for postnatal maturation of interneurons expressing parvalbumin (PV). FGFR1 is implicated in synapse formation in the hippocampus, and alterations in the expression of Fgfr1 and its ligand, Fgf2 accompany major depression. Understanding which cell types express Fgfr1 during development may elucidate its roles in normal development of the brain as well as illuminate possible causes of certain neuropsychiatric disorders.MethodsHere, we used a BAC transgenic reporter line to trace Fgfr1 expression in the developing postnatal murine CNS. The specific transgenic line employed was created by the GENSAT project, tgFGFR1-EGFPGP338Gsat, and includes a gene encoding enhanced green fluorescent protein (EGFP) under the regulation of the Fgfr1 promoter, to trace Fgfr1 expression in the developing CNS. Unbiased stereological counts were performed for several cell types in the cortex and hippocampus.ResultsThis model reveals that Fgfr1 is primarily expressed in glial cells, in both astrocytes and oligodendrocytes, along with some neurons. Dual labeling experiments indicate that the proportion of GFP+ (Fgfr1+) cells that are also GFAP+ increases from postnatal day 7 (P7) to 1 month, illuminating dynamic changes in Fgfr1 expression during postnatal development of the cortex. In postnatal neurogenic areas, GFP expression was also observed in SOX2, doublecortin (DCX), and brain lipid-binding protein (BLBP) expressing cells. Fgfr1 is also highly expressed in DCX positive cells of the dentate gyrus (DG), but not in the rostral migratory stream. Fgfr1 driven GFP was also observed in tanycytes and GFAP+ cells of the hypothalamus, as well as in Bergmann glia and astrocytes of the cerebellum.ConclusionsThe tgFGFR1-EGFPGP338Gsat mouse model expresses GFP that is congruent with known functions of FGFR1, including hippocampal development, glial cell development, and stem cell proliferation. Understanding which cell types express Fgfr1 may elucidate its role in neuropsychiatric disorders and brain development.

Tanycyte Gene Expression Dynamics in the Regulation of Energy Homeostasis

“…Still related to their transporter properties, GLUT1–known as facilitated glucose transporter member 1 ( Slc2a1 )–is expressed in β 1 tanycytes and, to a lesser extent, in β 2 tanycytes (34–36). β tanycytes have also restricted expression of neural stem markers such as Sox2 (16, 17, 37, 38) , Fgf-10 (17, 39, 40), Blbp (17), and Musashi1 (17), as well as several growth factor receptor genes, such as Fgfr1 (38, 41) and Cntfr (42), consistent with their stem/ progenitor cell function. In contrast, the gene markers of α tanycytes are more similar to non-tanycyte ependymal cells than β tanycytes.…”

FGF family members differentially regulate maturation and proliferation of stem cell-derived astrocytes

“…For example, FGF2 binds with a high affinity to FGFR1, while FGF18 preferentially binds to FGFR3 26,61 . In contrast to FGFR3, signaling through FGFR1 induces proliferation in both embryonic and human adult stem cells and is important for neurogenesis and proliferation and fate specification of radial glial cells in the cortex and hippocampus 62–65 . Our data also demonstrated that FGF2 treatment induced higher proliferation of astrocytes compared to FGF18 treatment.…”

Cross-Talk between Fibroblast Growth Factor Receptors and Other Cell Surface Proteins

“…While FGFR1 is widely found in the hippocampus and in various parts of the cortex, FGFR2 and FGFR3 proteins are scattered throughout the CNS, and their expression profile changes with the brain development. FGFR4 is less abundant than other FGFRs and is mainly localized to the medial habenular nucleus [44,45,46,47,48]. The FGFRs are involved in the development, function and maintenance of the CNS [49].…”