Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
J Comp Neurol. 2010 Apr 15;518(8):1232-48. doi: 10.1002/cne.22271.
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 E15.5. 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.
γ-氨基丁酸（GABA）能中间神经元在调节大脑皮层活动方面起着至关重要的作用，其功能障碍与精神分裂症和癫痫等神经疾病有关。这些细胞起源于脑室端神经节（GE）的腹侧端脑，并进行切线迁移进入皮层。目前，对于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，比较了正在积极迁移到皮层的 GABA 能中间神经元与 GE 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）转基因小鼠胚胎大脑中的皮层和 GE 进行荧光激活细胞分选，分离出纯的 GABA 能细胞群体。我们的微阵列分析鉴定出了许多在 E13.5 和 E15.5 时在迁移的皮质中间神经元中上调的新基因。其中许多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，鉴定出的几个基因参与迁移过程的调节，例如神经突生长、细胞黏附和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，这些数据为阐明中间神经元迁移的复杂性的未来研究提供了框架，并可能揭示与特定神经疾病发展相关的重要基因。
