Regulation of Cortical Neuron Migration by the Reelin Signaling Pathway
Regulation of Cortical Neuron Migration by the Reelin Signaling Pathway
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DOI：
10.1007/s11064-011-0407-4
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Nakajima, Kazunori
中科院分区：
文献类型：
--
作者：
Honda, Takao;Kobayashi, Kazuma;Nakajima, Kazunori
Reeler是一种中枢神经系统分层结构（如大脑皮层、海马和小脑）缺陷的突变小鼠，半个多世纪来一直受到广泛研究。全长cDNA的负责基因reeler，reelin，偶然发现，揭示了Reelin编码一个大的分泌蛋白。到目前为止，两种Reelin受体，载脂蛋白E受体2和极低密度脂蛋白受体，以及细胞质衔接蛋白Disabled同系物1（Dab 1）已被证明是Reelin信号传导所必需的。虽然一些下游级联Dab 1也被报道使用各种实验系统，在体内的生理功能的Reelin仍然存在争议。在这里，我们回顾了最近的进展，了解Reelin-Dab 1信号通路在发育中的大脑皮层。神经递质谷氨酸和抑制性中间神经元，其分泌γ-氨基丁酸（GABA）作为其主要神经递质。由于它们的出生地与它们最终居住的地点不同，这些神经元必须迁移到它们的最终目的地才能正确地发挥它们的功能。谷氨酸能神经元产生于大脑皮层（软腭）的脑室区（VZ）或脑室下区（SVZ），并向软膜表面径向迁移[1，2]，而抑制性中间神经元产生于端脑腹侧的神经节隆起，并向大脑皮层切向迁移[2，3]。通过对突变小鼠、基因敲除小鼠和人类遗传性疾病的分析，已经逐渐确定了调节神经元协调迁移的关键分子[4，5]。其中，Reelin是皮质神经元正确定位的重要分子[6]。虽然Reelin的功能已被广泛研究，但Reelin如何调节神经元的定位仍不清楚。在这篇综述中，我们提供了一个概述的神经解剖学异常的大脑皮层的reeler突变小鼠，总结了目前的理解的Reelin信号通路，并讨论了Reelin在体内的功能。
Reeler is a mutant mouse with defects in layered structures of the central nervous system, such as the cerebral cortex, hippocampus, and cerebellum, and has been extensively examined for more than half a century. The full-length cDNA for the responsible gene for reeler, reelin, was serendipitously identified, revealing that Reelin encodes a large secreted protein. So far, two Reelin receptors, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, and the cytoplasmic adaptor protein Disabled homolog 1 (Dab1) have been shown to be essential for Reelin signaling. Although a number of downstream cascades of Dab1 have also been reported using various experimental systems, the physiological functions of Reelin in vivo remain controversial. Here, we review recent advances in the understanding of the Reelin-Dab1 signaling pathway in the developing cerebral cortex. neurotransmitter glutamate, and inhibitory interneurons, which secrete gamma-aminobutyric-acid (GABA) as their primary neurotransmitter. Since their birthplaces are different from the sites where they eventually reside, these neurons must migrate to their final destinations to exert their functions correctly. Glutamatergic neurons are produced in the ventricular zone (VZ) or subventricular zone (SVZ) of the cerebral cortex (pallium) and migrate radially toward the pial surface [1, 2], whereas inhibitory interneurons are produced in the ganglionic eminences in the ventral telencephalon and migrate tangentially toward the cerebral cortex [2, 3]. From analyses of mutant mice, knockout mice, and human hereditary diseases, key molecules that regulate the orchestrated migration of neurons have been gradually identified [4, 5]. Among them, Reelin is an essential molecule for the proper positioning of cortical neurons [6]. Although the functions of Reelin have been extensively examined, how Reelin regulates the positioning of neurons remains unclear. In this review, we provide an overview of the neuroanatomical abnormalities of the cerebral cortex in reeler mutant mice, summarize the current understanding of the Reelin signaling pathway, and discuss Reelin functions in vivo.