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

BACKGROUND

Fibroblast 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 and its ligand, accompany major depression. Understanding which cell types express during development may elucidate its roles in normal development of the brain as well as illuminate possible causes of certain neuropsychiatric disorders.

METHODS

Here, we used a BAC transgenic reporter line to trace expression in the developing postnatal murine CNS. The specific transgenic line employed was created by the GENSAT project, , and includes a gene encoding enhanced green fluorescent protein () under the regulation of the promoter, to trace expression in the developing CNS. Unbiased stereological counts were performed for several cell types in the cortex and hippocampus.

RESULTS

This model reveals that is primarily expressed in glial cells, in both astrocytes and oligodendrocytes, along with some neurons. Dual labeling experiments indicate that the proportion of GFP+ (+) cells that are also GFAP+ increases from postnatal day 7 (P7) to 1 month, illuminating dynamic changes in 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. is also highly expressed in DCX positive cells of the dentate gyrus (DG), but not in the rostral migratory stream. driven GFP was also observed in tanycytes and GFAP+ cells of the hypothalamus, as well as in Bergmann glia and astrocytes of the cerebellum.

CONCLUSIONS

The 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 may elucidate its role in neuropsychiatric disorders and brain development.