Fibroblast Growth Factor 2 Regulates Astrocyte Differentiation in a Region-Specific Manner in the Hindbrain
Fibroblast Growth Factor 2 Regulates Astrocyte Differentiation in a Region-Specific Manner in the Hindbrain
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DOI：
10.1002/glia.21141
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发表时间：
2011-05-01
期刊：
影响因子：
6.2
通讯作者：
Unsicker, Klaus
中科院分区：
文献类型：
--
作者：
Irmady, Krithi;Zechel, Sabrina;Unsicker, Klaus
成纤维细胞生长因子-2在神经元和神经胶质细胞中具有重要的多效性，在各种生理和病理过程中发挥重要作用。为探讨内源性成纤维细胞生长因子-2在星形胶质细胞分化中的作用，我们研究了成纤维细胞生长因子-2缺失小鼠后脑内胶质纤维酸性蛋白的表达。在成年和发育中的成纤维细胞生长因子-2缺失小鼠的后脑中，GFAP以区域特异性的方式急剧减少，而星形胶质细胞的替代标志物的表达没有相关的变化。脑桥和延髓灰质的星形胶质细胞有明显的缺失，而白质则不明显。灰质和白质星形胶质细胞以不同的方式表达成纤维细胞生长因子-2和成纤维细胞生长因子受体。与GFAP启动子STAT(信号转导和转录激活因子)结合部位相关的组蛋白H3赖氨酸4残基(H3K4me2)甲基化显著减少，提示在体内星形胶质细胞分化的表观遗传调控中，FGF2起作用。这些观察结果强调了成纤维细胞生长因子-2在后脑星形胶质细胞分化中的重要性，以及星形胶质细胞对成纤维细胞生长因子-2作为分化诱导信号的需求的异质性。(C)2011年Wiley-Liss，Inc.
Fibroblast growth factor (FGF)-2 is known to have important pleiotropic effects in neuronal and glial cells during various physiological and pathological events. To investigate the role of endogenous FGF-2 in the differentiation of astrocytes, we studied the expression of glial fibrillary acidic protein (GFAP) in the hindbrain of the FGF-2 null mouse. GFAP was drastically decreased in a region-specific manner in the hindbrain of the adult and developing FGF-2 null mouse without an associated change in the expression of alternate markers for astrocytes. The deficit was evident in the astrocytes of pontine and medullary gray matter but not in the white matter. The astrocytes of the gray and white matter were seen to express FGF-2 and FGF receptors in a distinct pattern. The methylation of histone H3 at lysine 4 residue (H3K4me2) associated with the STAT (signal transducer and activator of transcription)binding site of the GFAP promoter was significantly decreased in the gray matter of the FGF-2 null mouse, suggesting a role for FGF-2 in the epigenetic regulation of astrocyte differentiation in vivo. These observations underscore the importance of FGF-2 in astroglial differentiation in the hindbrain and the heterogeneity of astrocytes in their requirement for FGF-2 as a differentiation inducing signal. (c) 2011 Wiley-Liss, Inc.