Differential Gene Expression in Migrating Cortical Interneurons During Mouse Forebrain Development
Differential Gene Expression in Migrating Cortical Interneurons During Mouse Forebrain Development
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DOI：
10.1002/cne.22271
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发表时间：
2010-04-15
影响因子：
2.5
通讯作者：
Parnavelas, John G.
中科院分区：
文献类型：
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作者：
Faux, Clare;Rakic, Sonja;Parnavelas, John G.
γ-氨基丁酸 (GABA) 能中间神经元在调节大脑皮层的活动中发挥着至关重要的作用，其功能的破坏与精神分裂症和癫痫等神经系统疾病有关。这些细胞起源于腹侧端脑的神经节隆起（GE），并经历切向迁移进入皮质。目前，人们对调节中间神经元迁移的信号机制知之甚少。因此，我们进行了微阵列分析，比较了主动迁移到皮质中的 GABA 能中间神经元与 GE 中的 GABA 能中间神经元之间的基因表达变化。我们能够通过对谷氨酸脱羧酶 67 (GAD67)-绿色荧光蛋白 (GFP) 转基因小鼠胚胎脑中的皮质和 GE 进行荧光激活细胞分选，分离出纯 GABA 细胞群。我们的微阵列分析发现了许多新基因，这些基因在 E13.5 和 E 15.5 的迁移皮质中间神经元中上调。许多这些基因先前已被证明在神经元和非神经元细胞类型的细胞迁移中发挥作用。此外，一些已确定的基因参与迁移过程的调节，例如神经突生长、细胞粘附以及肌动蛋白细胞骨架和微管网络的重塑。此外，定量聚合酶链反应和原位杂交分析证实，其中一些基因的表达仅限于皮质中间神经元。因此，这些数据为未来的研究提供了一个框架，旨在阐明中间神经元迁移的复杂性，进而可能揭示与特定神经系统疾病的发展相关的重要基因。 J. Comp Neurol 5 18:1232-1248, 2010 (C) 2009 Wiley-Liss, Inc
gamma-Aminobutyric acid (GABA)ergic interneurons play a vital role in modulating the activity of the cerebral cortex, and disruptions to their function have been linked to neurological disorders such as schizophrenia and epilepsy. These cells originate in the ganglionic eminences (GE) of the ventral telencephalon and undergo tangential migration to enter the cortex Currently, little is known about the signaling mechanisms that regulate interneuron migration. We therefore performed a microarray analysis comparing the changes in gene expression between the GABAergic interneurons that are actively migrating into the cortex with those in the GE. We were able to isolate pure populations of GABAergic cells by fluorescence-activated cell sorting of cortex and GE from embryonic brains of glutamate decarboxylase 67 (GAD67)-green fluorescent protein (GFP) transgenic mice Our microarray analysis identified a number of novel genes that were upregulated in migrating cortical interneurons at both E13.5 and E 15.5. Many of these genes have previously been shown to play a role in cell migration of both neuronal and non-neuronal cell types. In addition, several of the genes identified are involved in the regulation of migratory processes, such as neurite outgrowth, cell adhesion, and remodeling of the actin cytoskeleton and microtubule network. Moreover, quantitative polymerase chain reaction and in situ hybridization analyses confirmed that the expression of some of these genes is restricted to cortical interneurons. These data therefore provide a framework for future studies aimed at elucidating the complexities of interneuron migration and, in turn, may reveal important genes that are related to the development of specific neurological disorders. J. Comp Neurol 5 18:1232-1248, 2010 (C) 2009 Wiley-Liss, Inc