Noctor S C, Flint A C, Weissman T A, Dammerman R S, Kriegstein A R
Department of Neurology, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
Nature. 2001 Feb 8;409(6821):714-20. doi: 10.1038/35055553.
The neocortex of the adult brain consists of neurons and glia that are generated by precursor cells of the embryonic ventricular zone. In general, glia are generated after neurons during development, but radial glia are an exception to this rule. Radial glia are generated before neurogenesis and guide neuronal migration. Radial glia are mitotically active throughout neurogenesis, and disappear or become astrocytes when neuronal migration is complete. Although the lineage relationships of cortical neurons and glia have been explored, the clonal relationship of radial glia to other cortical cells remains unknown. It has been suggested that radial glia may be neuronal precursors, but this has not been demonstrated in vivo. We have used a retroviral vector encoding enhanced green fluorescent protein to label precursor cells in vivo and have examined clones 1-3 days later using morphological, immunohistochemical and electrophysiological techniques. Here we show that clones consist of mitotic radial glia and postmitotic neurons, and that neurons migrate along clonally related radial glia. Time-lapse images show that proliferative radial glia generate neurons. Our results support the concept that a lineage relationship between neurons and proliferative radial glia may underlie the radial organization of neocortex.
成年大脑的新皮质由胚胎脑室区的前体细胞产生的神经元和神经胶质细胞组成。一般来说,神经胶质细胞在发育过程中是在神经元之后产生的,但放射状胶质细胞是这一规律的例外。放射状胶质细胞在神经发生之前产生,并引导神经元迁移。放射状胶质细胞在整个神经发生过程中都具有有丝分裂活性,当神经元迁移完成时消失或变成星形胶质细胞。尽管已经探索了皮质神经元和神经胶质细胞的谱系关系,但放射状胶质细胞与其他皮质细胞的克隆关系仍然未知。有人提出放射状胶质细胞可能是神经元前体,但这一点在体内尚未得到证实。我们使用了一种编码增强型绿色荧光蛋白的逆转录病毒载体在体内标记前体细胞,并在1 - 3天后使用形态学、免疫组织化学和电生理技术检查克隆。在这里我们表明,克隆由有丝分裂的放射状胶质细胞和有丝分裂后的神经元组成,并且神经元沿着克隆相关的放射状胶质细胞迁移。延时图像显示增殖性放射状胶质细胞产生神经元。我们的结果支持这样一种概念,即神经元与增殖性放射状胶质细胞之间的谱系关系可能是新皮质放射状组织的基础。