Neurogenic radial glia in the outer subventricular zone of human neocortex
Neurogenic radial glia in the outer subventricular zone of human neocortex
复制标题
DOI：
10.1038/nature08845
复制
发表时间：
2010-03-25
期刊：
影响因子：
64.8
通讯作者：
Kriegstein, Arnold R.
中科院分区：
文献类型：
--
作者：
Hansen, David V.;Lui, Jan H.;Kriegstein, Arnold R.
发育中的啮齿动物皮层中的神经元是由具有神经干细胞功能的放射状胶质细胞产生的。这些上皮细胞排列在脑室内，产生中间祖细胞，这些祖细胞迁移到脑室下区（SVZ）并增殖以增加神经元数量。发育中的人类SVZ有一个大规模扩展的外区（OSVZ），被认为有助于皮质的大小和复杂性。然而，OSVZ祖细胞类型及其对神经发生的贡献尚不清楚。在这里，我们发现大量的放射状胶质样细胞和中间祖细胞填充人类OSVZ。我们发现OSVZ径向胶质样细胞有一个很长的基底突起，但令人惊讶的是，它们不是上皮细胞，因为它们缺乏与心室表面的接触。通过实时成像和克隆分析，我们证明这些细胞可以进行增殖分裂和自我更新的不对称分裂，以产生可以进一步增殖的神经祖细胞。我们还发现，抑制OSVZ祖细胞中的Notch信号传导可诱导其神经元分化。非脑室放射状胶质样细胞的建立可能是人类大脑皮层大小和复杂性增加的关键进化进展。
Neurons in the developing rodent cortex are generated from radial glial cells that function as neural stem cells. These epithelial cells line the cerebral ventricles and generate intermediate progenitor cells that migrate into the subventricular zone (SVZ) and proliferate to increase neuronal number. The developing human SVZ has a massively expanded outer region (OSVZ) thought to contribute to cortical size and complexity. However, OSVZ progenitor cell types and their contribution to neurogenesis are not well understood. Here we show that large numbers of radial glia-like cells and intermediate progenitor cells populate the human OSVZ. We find that OSVZ radial glia-like cells have a long basal process but, surprisingly, are non-epithelial as they lack contact with the ventricular surface. Using real-time imaging and clonal analysis, we demonstrate that these cells can undergo proliferative divisions and self-renewing asymmetric divisions to generate neuronal progenitor cells that can proliferate further. We also show that inhibition of Notch signalling in OSVZ progenitor cells induces their neuronal differentiation. The establishment of non-ventricular radial glia-like cells may have been a critical evolutionary advance underlying increased cortical size and complexity in the human brain.