Sonic hedgehog-regulateld oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system

Sonic hedgehog-regulateld oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system
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DOI:
10.1016/s0896-6273(00)80897-1
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发表时间:
2000-02-01
期刊:
影响因子:
16.2
通讯作者:
Rowitch, DH
Rowitch, DH
中科院分区:
医学1区
文献类型:
--
作者:
Lu, QR;Yuk, DI;Rowitch, DH

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在发育过程中,碱性螺旋-环-螺旋(bHLH)蛋白调节多能祖细胞神经元的形成。然而,bHLH因子与胶质细胞生成的联系尚未被描述。我们已经分离出一对少突胶质细胞谱系基因(Olg-1和Olg-2),它们编码bHLH蛋白,并与脊椎动物中枢神经系统(CNS)中少突胶质细胞的发育密切相关。Olg-1在大鼠皮质祖细胞培养物中的异位表达促进少突胶质细胞前体的形成。在发育中的小鼠胚胎中,Olg基因表达与少突胶质细胞谱系最早的已知标记重叠,但先于这些标记。Olg基因表达于中脑-间脑边界和邻近底板,这是分泌的信号分子Sonic hedgehog(Shh)的来源。在转基因小鼠中的获得和丧失功能的分析表明,Shh是必要的和足够的Olg基因在体内的表达。
During development, basic helix-loop-helix (bHLH) proteins regulate formation of neurons from multipotent progenitor cells. However, bHLH factors linked to gliogenesis have not been described. We have isolated a pair of oligodendrocyte lineage genes (Olg-1 and Olg-2) that encode bHLH proteins and are tightly associated with development of oligodendrocytes in the vertebrate central nervous system (CNS). Ectopic expression of Olg-1 in rat cortical progenitor cell cultures promotes formation of oligodendrocyte precursors. In developing mouse embryos, Olg gene expression overlaps but precedes the earliest known markers of the oligodendrocyte lineage. Olg genes are expressed at the tetencephalon-diencephalon border and adjacent to the floor plate, a source of the secreted signaling molecule Sonic hedgehog (Shh). Gain- and loss-of-function analyses in transgenic mice demonstrate that Shh is both necessary and sufficient for Olg gene expression in vivo.