Development and migration of GABAergic neurons in the mouse myelencephalon

Development and migration of GABAergic neurons in the mouse myelencephalon
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DOI:
10.1002/cne.21380
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发表时间:
2007-07-10
影响因子:
2.5
通讯作者:
Murakami, Fujio
Murakami, Fujio
中科院分区:
医学3区
文献类型:
--
作者:
Tashiro, Yasura;Yanagawa, Yuchio;Murakami, Fujio

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GABA能神经元是广泛分布于中枢神经系统的主要抑制性中间神经元。已经确定的是,它们起源于胚胎前脑发育过程中的一个焦点区域,然后迁移到其他区域,如新皮质。然而,GABA能神经元的迁移在大脑的其他轴向水平仍然不清楚。我们使用谷氨酸脱羧酶67 /绿色荧光蛋白(GAD 67-GFP)基因敲入小鼠研究了中脑GABA能神经元的早期发育。固定组织的冠状切片和平坦的整装标本的观察表明,虽然GFP阳性细胞在早期阶段仅限于中脑腹侧的软膜下区域,但随着发育的进行,它们向背侧扩散并最终占据中脑的整个区域。我们开发了一种平板安装在体外制备,其中这些模式的发展可以概括。将野生型胚胎的背侧中脑组织移植到GAD 67-GFP小鼠胚胎的相应区域清楚地证明了从宿主到供体组织的背侧定向GABA能神经元的侵入。这些结果表明,腹到背切向迁移的GABA能神经元发生在中脑。我们的研究结果扩展了前脑中的观察,即特定脑区室中的抑制性和兴奋性神经元采取不同的迁移路径。
GABAergic neurons are the major inhibitory interneurons that are widely distributed in the central nervous system. It is well established that they originate from a focal region in the embryonic forebrain during development, and then migrate to other regions such as the neocortex. However, the migration of GABAergic neurons remains obscure in other axial levels of the brain. We examined the early development of myelencephalic GABAergic neurons using glutamate decarboxylase 67 / green fluorescent protein (GAD67-GFP) knockin mice. Observation of fixed tissues in coronal sections and flat whole-mount preparations indicated that, while GFP-positive cells are restricted to the subpial region in the ventral aspect of the myelencephalon at an early stage, they spread dorsally and eventually occupy the entire region of the myelencephalon as development proceeds. We developed a flat-mount in vitro preparation in which these patterns of development could be recapitulated. Transplantation of dorsal myelencephalic tissue of a wildtype embryo to a corresponding region of GAD67-GFP mouse embryos clearly demonstrated invasion of dorsally oriented GABAergic neurons from host to donor tissue. These results indicate that ventral-to-dorsal tangential migration of GABAergic neurons takes place in the myelencephalon. Our results extend the observations in the forebrain that inhibitory and excitatory neurons in a specific brain compartment take distinct migratory paths.