Hack M A, Sugimori M, Lundberg C, Nakafuku M, Götz M
Neuronal Specification, Max-Planck-Institute of Neurobiology, D-82152 Martinsried, Germany.
Mol Cell Neurosci. 2004 Apr;25(4):664-78. doi: 10.1016/j.mcn.2003.12.012.
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.
神经球培养被广泛用于增殖多能中枢神经系统前体细胞，但其向神经元或少突胶质细胞的分化能力较差。为了阐明该系统中的命运决定机制，我们研究了在发育和成年期从不同中枢神经系统区域衍生而来的神经球中候选转录因子的表达和功能。我们观察到，在神经球培养中，当生长因子暴露时，端脑前体细胞中存在的大多数转录因子显著下调，而Olig1和Olig2的表达则强烈上调。对神经球中Olig2的干扰揭示了其在扩增过程中的自我更新以及分化过程中神经元和少突胶质细胞生成中的作用。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的过表达足以将几乎所有神经球衍生细胞导向神经发生。因此，在神经球培养模型中激活了一条结合背侧和腹侧区域转录因子的途径。
