Regionalization and fate specification in neurospheres:: the role of Olig2 and Pax6
Regionalization and fate specification in neurospheres:: the role of Olig2 and Pax6
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DOI：
10.1016/j.mcn.2003.12.012
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发表时间：
2004-04-01
影响因子：
3.5
通讯作者：
Götz, M
中科院分区：
文献类型：
--
作者：
Hack, MA;Sugimori, M;Götz, M
神经球培养被广泛用于增殖多能CNS前体细胞，但它们向神经元或少突胶质细胞的分化相当差。为了阐明在这个系统中的命运决定，我们研究了候选转录因子的表达和功能的神经球来自不同的中枢神经系统区域在发展和成年。我们观察到显着下调大多数转录因子存在于端脑前体细胞生长因子暴露后，在神经球文化，而Olig1和Olig2的表达强烈上调。在神经球中Olig2的干扰揭示了其在扩张过程中的自我更新以及在分化过程中神经元和少突胶质细胞的生成中的作用。我们进一步表明，在神经球培养系统中，神经发生完全依赖于Pax6，与起源区域无关，并且Pax6过表达足以指导几乎所有神经球源性细胞朝向神经发生。因此，在神经球培养模型中，结合背侧和腹侧区域的转录因子的途径被激活。(C)2004年爱思唯尔公司All rights reserved.
Neurosphere cultures are widely used to propagate multipotent CNS precursors, but their differentiation into neurons or oligodendrocytes is rather poor. To elucidate fate determination in this system, we examined the expression and function of candidate transcription factors in neurospheres derived from different CNS regions during development and adulthood. We observed prominent down-regulation of most transcription factors present in telencephalic precursors upon growth factor exposure in neurosphere cultures while Olig1 and Olig2 expression was strongly up-regulated. Interference with Olig2 in neurospheres revealed its role in self-renewal during expansion and for the generation of neurons and oligodendrocytes during differentiation. We further show that neurogenesis becomes fully Pax6-dependent in the neurosphere culture system, independent of the region of origin, and that Pax6 overexpression is sufficient to direct almost all neurosphere-derived cells towards neurogenesis. Thus, a pathway combining transcription factors of dorsal and ventral regions is activated in the neurosphere culture model. (C) 2004 Elsevier Inc. All rights reserved.