The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon
The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon
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DOI：
10.1074/jbc.m512669200
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发表时间：
2006-05-12
影响因子：
4.8
通讯作者：
Okuda, A
中科院分区：
文献类型：
--
作者：
Miyagi, S;Nishimoto, M;Okuda, A
Sox 2在神经上皮干细胞中高水平表达，并在整个成年期持续存在于神经干/祖细胞中。我们先前表明，Sox 2调节区2（SRR 2）驱动这些细胞中的强表达。在这里，我们产生了转基因小鼠品系与β- geo报告基因的控制下的SRR 2，以检查时空功能的这一调控区。我们发现SRR 2在神经干/祖细胞中具有特异性功能。然而，与Nestin第二内含子增强子不同，SRR 2显示出仅在端脑的限制区域中发挥作用的强区域特异性，而不在中枢神经系统的任何其他部分如脊髓中发挥作用。我们还通过体外克隆形成试验表明，这些SRR 2功能细胞中至少有一部分具有神经干细胞的标志性特性。在成人脑中，我们可以检测到在侧脑室的脑室下区和沿着活跃分裂细胞所在的吻侧迁移流中强烈的β- geo表达。染色质免疫沉淀分析揭示了POU和Sox因子与神经干/祖细胞中SRR 2的相互作用。我们的数据还表明，这些蛋白质的特异性招聘的SRR 2在端脑定义的时空活动的增强子在发育中的神经系统。
Sox2 is expressed at high levels in neuroepithelial stem cells and persists in neural stem/ progenitor cells throughout adulthood. We showed previously that the Sox2 regulatory region 2 ( SRR2) drives strong expression in these cells. Here we generated transgenic mouse strains with the beta- geo reporter gene under the control of the SRR2 in order to examine the spatiotemporal function of this regulatory region. We show that the SRR2 functions specifically in neural stem/ progenitor cells. However, unlike Nestin 2nd intronic enhancer, the SRR2 shows strong regional specificity functioning only in restricted areas of the telencephalon but not in any other portions of the central nervous system such as the spinal cord. We also show by in vitro clonogenic assay that at least some of these SRR2- functioning cells possess the hallmark properties of neural stem cells. In adult brains, we could detect strong beta- geo expression in the subventricular zone of the lateral ventricle and along the rostral migrating stream where actively dividing cells reside. Chromatin immunoprecipitation assays reveal interactions of POU and Sox factors with SRR2 in neural stem/ progenitor cells. Our data also suggest that the specific recruitment of these proteins to the SRR2 in the telencephalon defines the spatiotemporal activity of the enhancer in the developing nervous system.