-Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system.
-Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system.
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作者：
Collette JC;Choubey L;Smith KM
成纤维细胞生长因子（FGF）及其受体（FGFR）参与多个器官和器官系统的发育和功能，包括中枢神经系统（CNS）。 FGFR1（中枢神经系统中表达的三种 FGFR 之一）通过 FGFR1 进行 FGF 信号传导，在产前和产后神经发生过程中刺激干细胞增殖，并参与调节大脑许多发育区域的细胞类型比例。 FGFR1 信号传导异常与某些神经精神疾病有关。通过原位杂交，Fgfr1 表达已被证明在整个胚胎和出生后大脑发育过程中在空间和时间上发生变化。然而，原位杂交缺乏足够的分辨率来鉴定哪些细胞类型直接参与 FGF 信号传导。此外，由于针对 FGFR1 的抗体通常会与 FGFR 家族的其他成员发生交叉反应，因此单独的免疫细胞化学不足以准确记录 Fgfr1 的表达。在这里，我们阐明了胚胎和围产期小鼠大脑中 Fgfr1 表达细胞的身份。为此，我们利用了从 GENSAT 项目获得的 tgFGFR1-EGFPGP338Gsat BAC 线 (tgFgfr1-EGFP+)。 tgFgfr1-EGFP+ 系在 Fgfr1 启动子的控制下表达 EGFP，从而使内源表达 Fgfr1 的细胞也呈现阳性 GFP 信号。通过使用 GFP 抗体和细胞类型特异性抗体进行简单的免疫染色，我们能够准确确定 Fgfr1 表达细胞的细胞类型。这项技术揭示了 Fgfr1 在含有 BLBP+ 放射状胶质干细胞的增殖区（例如 E14.5 小鼠的皮质和海马脑室区以及小脑原基）以及 DCX+ 成神经细胞中的表达。此外，我们的数据揭示了 P0.5 小鼠前中线、海马、皮质、下丘脑和小脑的 BLBP+ 细胞以及前中线早期形成的 GFAP+ 星形胶质细胞的增殖区中 Fgfr1 的表达。了解 Fgfr1 在发育过程中何时以及在何处表达对于提高我们对其在神经发育过程以及成熟中枢神经系统中的功能的理解至关重要。这一信息有一天可能会为理解神经精神疾病中异常 FGF 信号传导的参与提供一条发现途径。
Fibroblast 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. Fgfr1 expression has been shown, via in situ hybridization, to vary spatially and temporally throughout embryonic and postnatal development of the brain. However, in situ hybridization 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 document Fgfr1 expression. Here, we elucidate the identity of Fgfr1 expressing cells in both the embryonic and perinatal mouse brain. To do this, we utilized a tgFGFR1-EGFPGP338Gsat BAC line (tgFgfr1-EGFP+) obtained from the GENSAT project. The tgFgfr1-EGFP+ line expresses EGFP under the control of a Fgfr1 promoter, thereby causing cells endogenously expressing Fgfr1 to 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 of Fgfr1 expressing cells. This technique revealed Fgfr1 expression 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 reveal Fgfr1 expression 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. Understanding when during development and where Fgfr1 is 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.