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Neurogenesis of GABAergic neurons in the neocortex

新皮质中 GABA 能神经元的神经发生

基本信息

批准号：
14380366
负责人：
TAMAMAKI Nobuaki
金额：
$ 10.82万
依托单位：
Kumamoto University (2004)Kyoto University (2002-2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

In the developing rodent neocortex, the glutamatergic neurons are supplied by proliferation of radial glias in the ventricular zone(VZ) of the pallium, while the GABAergic neurons are produced in the the ganglionic eminence(GE), a subpallial structure, and then come into the neocortex by tangential cell migration. However, cell lineage analyses with a retrovirus have often revealed clonally related GABAergic neuron pairs located closely within the neocortex. Following these reports, we speculated that some of the GABAergic neurons were produced in the rodent neocortex. In GAD67-GFP knock-in mice, we found colocalization of single-pulse (30 min) BrdU and GFP, or Ki-67 and GFP in the subventricular zone(SVZ)and the intermediate zone(IZ) of the neocortex at birth. One forth of GFP-positive cells in the SVZ and the IZ were positive for Ki-67. And one thirds of GFP-positive cells in the neocortex were positive for nestin. These data indicate that a portion of GAD67-positivecells are proliferative, suggesting these cells are the progenitorscommitted to GABAergic neurons. To assess whether the putative progenitors for GABAergic neurons were also supplied by tangential cellmigration from the GE, we injected an adenovirus or retrovirus witha construct (CA promoter-loxP-GFP-loxP) into the ventricle of Emx1-Cre knock-in mouse embryos : These viruses reveal the origin of the Emx1-negative cells in the neocortex. We found some of the putative GABAergic neuron progenitors in the neocortex were in Emx1-negativelineage and derived from the subpallial VZ. We conclude that the GABAergic neurons in the rodent neocortex are supplied not only by migration of postmitotic GABAergic neurons from the GE, but also by proliferation of their progenitors immigrated from the GE to the neocortex.

在发育中的啮齿动物新皮质中，谷氨酸能神经元由大脑皮层心室区（VZ）中放射状胶质细胞的增殖提供，而GABA能神经元在大脑皮层下结构的神经节隆起（GE）中产生，然后通过切向细胞迁移进入新皮质。然而，逆转录病毒的细胞谱系分析经常揭示出位于新皮质内的克隆相关的 GABA 能神经元对。根据这些报告，我们推测一些 GABA 能神经元是在啮齿动物新皮质中产生的。在 GAD67-GFP 敲入小鼠中，我们发现单脉冲（30 分钟）BrdU 和 GFP 或 Ki-67 和 GFP 在出生时新皮质的室下区（SVZ）和中间区（IZ）共定位。 SVZ 和 IZ 中四分之一的 GFP 阳性细胞对 Ki-67 呈阳性。新皮质中三分之一的 GFP 阳性细胞的巢蛋白呈阳性。这些数据表明一部分 GAD67 阳性细胞正在增殖，表明这些细胞是 GABA 能神经元的祖细胞。为了评估 GABA 能神经元的假定祖细胞是否也由 GE 的切向细胞迁移提供，我们将腺病毒或带有构建体（CA 启动子-loxP-GFP-loxP）的逆转录病毒注射到 Emx1-Cre 敲入小鼠胚胎的心室中：这些病毒揭示了新皮质中 Emx1 阴性细胞的起源。我们发现新皮质中一些假定的 GABA 能神经元祖细胞属于 Emx1 阴性谱系，并且源自大脑皮层下 VZ。我们得出的结论是，啮齿动物新皮质中的 GABA 能神经元不仅由来自 GE 的有丝分裂后 GABA 能神经元的迁移提供，而且还由从 GE 迁移到新皮质的祖细胞的增殖提供。