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.

在发展中的啮齿动物新皮层中，谷氨酸能神经元是通过pallium室（VZ）的径向纤维的扩散提供的，而Gabaergic神经元则在神经节感染性（GE）中产生，然后进入副层结构，然后进入副层结构，然后进入。通过切向细胞迁移的新皮层。然而，使用逆转录病毒的细胞谱系分析通常显示出与新皮层内紧密的克隆相关的GABA能神经元对。遵循这些报告，我们推测在啮齿动物新皮层中产生了一些GABA能神经元。在GAD67-GFP敲门小鼠中，我们发现了新皮层时在室脑室区（SVZ）（SVZ）（SVZ）和中间区（IZ）的单脉冲（30分钟）BRDU和GFP或GFP共定位。 SVZ和IZ中的GFP阳性细胞的一个对KI-67呈阳性。新皮层中的三分之一的GFP阳性细胞对巢蛋白呈阳性。这些数据表明，一部分GAD67-Positivecell是增殖性的，这表明这些细胞是对GABA能神经元的祖细胞的。为了评估GE的切向细胞移民是否还提供了用于GABA能神经元的假定祖细胞，我们向腺病毒或逆转录病毒注射了A构建体（CA启动子-Loxp-GFP-loxp）这些病毒揭示了新皮层中EMX1阴性细胞的起源。我们发现，新皮层中的一些推定的GABA能神经元祖细胞在EMX1-NEGATIVELINEAGE中，并源自下pallial VZ。我们得出的结论是，啮齿动物新皮层中的GABA能神经元不仅是通过从GE迁移的有丝分裂后GABA能神经元的迁移来提供的，而且还通过从GE向新皮层移民的祖细胞的增殖来提供。