Quantitative assessment of fibroblast growth factor receptor 1 expression in neurons and glia.
Quantitative assessment of fibroblast growth factor receptor 1 expression in neurons and glia.
复制标题
作者：
Choubey L;Collette JC;Smith KM
成纤维细胞生长因子(FGFs)及其受体(FGFRs)在发育和成人中枢神经系统(CNS)中具有多种功能。例如，FGFR1受体对皮质和海马区放射状胶质细胞的增殖和命运指定、少突胶质细胞的增殖和再生、中线胶质细胞形态和胞体易位、Bergmann胶质细胞形态和小脑形态发生都是重要的。此外，星形胶质细胞中的FGFR1信号是表达小白蛋白(PV)的中间神经元出生后成熟所必需的。FGFR1参与了海马区突触的形成，FGFR1及其配体FGF2表达的改变伴随着严重的抑郁症。了解哪些细胞类型在发育过程中表达FGFR1，可能会阐明其在大脑正常发育中的作用，并可能阐明某些神经精神疾病的可能原因。在这里，我们使用BAC转基因报告系来追踪FGFR1在发育中的小鼠中枢神经系统中的表达。所使用的特定转基因系由GENSAT计划创建，tgFGFR1-EGFPGP338Gsat，并包括一个在FGFR1启动子调控下编码增强型绿色荧光蛋白(EGFP)的基因，以追踪FGFR1在发育中的中枢神经系统中的表达。对大脑皮层和海马区的几种细胞类型进行了无偏的体视学计数。这一模型表明，FGFR1主要在胶质细胞、星形胶质细胞和少突胶质细胞以及一些神经元中表达。双重标记实验表明，GFP+(FGFR1+)细胞同时也是GFAP+的细胞比例从出生后第7天(P7)到1个月增加，说明了FGFR1表达在出生后皮质发育过程中的动态变化。在生后神经源区，SOX2、双皮质素(DCX)和脑脂结合蛋白(BLBP)表达细胞中也观察到GFP的表达。FGFR1在齿状回(DG)的DCX阳性细胞中也有高表达，但在吻端迁移流中不表达。在下丘脑的松弛细胞和GFAP+细胞以及小脑的Bergmann胶质细胞和星形胶质细胞中也观察到了FGFR1驱动的GFP。TgFGFR1-EGFPGP338Gsat小鼠模型表达的GFP与FGFR1的已知功能一致，包括海马区发育、胶质细胞发育和干细胞增殖。了解哪些细胞类型表达FGFR1可能会阐明其在神经精神障碍和脑发育中的作用。
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 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. Here, 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. This 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. The 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.