Multipotent stem cells from the mouse basal forebrain contribute GABAergic neurons and oligodendrocytes to the cerebral cortex during embryogenesis
Multipotent stem cells from the mouse basal forebrain contribute GABAergic neurons and oligodendrocytes to the cerebral cortex during embryogenesis
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DOI：
10.1523/jneurosci.21-22-08854.2001
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发表时间：
2001-11-15
影响因子：
5.3
通讯作者：
Temple, S
中科院分区：
文献类型：
--
作者：
He, WL;Ingraham, C;Temple, S
在中枢神经系统发育过程中，细胞迁移起着重要的作用，增加了不同区域细胞的复杂性。早期的研究表明，在胚胎时期，细胞从基底前脑迁移到上覆的背前脑。这些迁移细胞包括分布在大脑皮层和海马体中的gaba能神经元。在这项研究中，我们研究了迁移到前脑背侧的其他基底前脑细胞的命运，使用一种抗体来识别基底细胞，这种抗体可以识别dlx同源盒基因家族的早期（dlx1/2）和晚期（dlx 5/6）成员。我们发现皮层和海马少突胶质细胞的亚群也是腹侧衍生的。我们将这些细胞的起源追溯到能够产生gaba能神经元和少突胶质细胞的基底多能干细胞。克隆分析表明，相同胚胎年龄的基底前脑干细胞比背前脑干细胞产生更多的gaba能神经元。此外，来自基底前脑的干细胞克隆比来自背前脑的干细胞克隆更可能含有gaba能神经元和少突胶质细胞。这表明前脑干细胞是区域性的。虽然在培养的基底干细胞中未检测到dlx的表达，但这些细胞产生了能够迁移的dlx阳性产物。这些数据表明，发育中的大脑皮层包含了基底前脑的神经元和胶质产物，并表明这些迁移细胞来自一个共同的祖细胞，即一种dlx阴性的基底前脑干细胞。
During CNS development, cell migrations play an important role, adding to the cellular complexity of different regions. Earlier studies have shown a robust migration of cells from basal forebrain into the overlying dorsal forebrain during the embryonic period. These immigrant cells include GABAergic neurons that populate the cerebral cortex and hippocampus. In this study we have examined the fate of other basal forebrain cells that migrate into the dorsal forebrain, identifying basal cells using an antibody that recognizes both early (dlx1/2) and late (dlx 5/6) members of the dlx homeobox gene family. We found that a subpopulation of cortical and hippocampal oligodendrocytes are also ventral-derived. We traced the origin of these cells to basal multipotent stem cells capable of generating both GABAergic neurons and oligodendrocytes. A clonal analysis showed that basal forebrain stem cells produce significantly more GABAergic neurons than dorsal forebrain stem cells from the same embryonic age. Moreover, stem cell clones from basal forebrain are significantly more likely to contain both GABAergic neurons and oligodendrocytes than those from dorsal. This indicates that forebrain stem cells are regionally specified. Whereas dlx expression was not detected within basal stem cells growing in culture, these cells produced dlx-positive products that are capable of migration. These data indicate that the developing cerebral cortex incorporates both neuronal and glial products of basal forebrain and suggest that these immigrant cells arise from a common progenitor, a dlx-negative basal forebrain stem cell.