Neurogenin 3 Cellular and Subcellular Localization in the Developing and Adult Hippocampus
Neurogenin 3 Cellular and Subcellular Localization in the Developing and Adult Hippocampus
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DOI：
10.1002/cne.22304
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发表时间：
2010-05-15
影响因子：
2.5
通讯作者：
Arevalo, Maria-Angeles
中科院分区：
文献类型：
--
作者：
Simon-Areces, Julia;Membrive, Gema;Arevalo, Maria-Angeles
神经生成素3（Neurogenin 3，Ngn 3）是一个受Notch受体调控的前神经基因，参与海马神经元树突形态和突触可塑性的调控。在这里，我们报告的本地化和亚细胞分布的Ngn 3在海马在体内和神经元培养。原位杂交显示Ngn 3 mRNA在成年小鼠海马锥体层和齿状回表达。免疫组织化学研究显示，Ngn 3定位主要是在胚胎（E）17天和出生后（P）0天的海马隆起的细胞质。P10时，海马CA 1-CA 3区锥体神经元胞质内有阳性细胞，齿状回颗粒细胞胞核内有阳性细胞。在成年海马中，Ngn 3定位于锥体神经元和颗粒细胞的细胞核和细胞质中。在培养的海马神经元的发育过程中，Ngn 3 mRNA的表达是较高的神经元极化的阶段，通过逆转录聚合酶链反应（RT-PCR）判断，它主要是细胞质。在用表达myc-Ngn 3的病毒感染的神经元中追踪Ngn 3的亚细胞定位表明，该蛋白质在合成后迅速易位到细胞核，然后再转运到细胞质。用一种有效的和特异性的CRM 1输出抑制剂leptomycinB处理，诱导其积累到细胞核中，表明CRM 1介导Ngn 3的核输出。这些结果表明Ngn 3可能通过在细胞质中的作用在神经元发育中发挥作用。神经学比较杂志518：1814-1824，2010年。(C)2009威利-利斯公司
Neurogenin 3 (Ngn3), a proneural gene controlled by the Notch receptor, is implicated in the control of dendrite morphology and synaptic plasticity of cultured hippocampal neurons. Here we report the localization and subcellular distribution of Ngn3 in the hippocampus in vivo and in neuronal cultures. In situ hybridization showed Ngn3 mRNA expression in the pyramidal layer and dentate gyrus of adult mouse hippocampus. Immunohistochemistry studies revealed that Ngn3 localization is mostly cytoplasmic in the hippocampal eminence at embryonic day (E) 17 and postnatal day (P)0. At P10 it is cytoplasmic in CA1-CA3 pyramidal neurons and nuclear in granule cells of the dentate gyrus. In the adult hippocampus Ngn3 is localized in the nucleus and cytoplasm of both pyramidal neurons and granule cells. During development of cultured hippocampal neurons, Ngn3 mRNA expression is higher at stages of neuronal polarization, as judged by reverse-transcription polymerase chain reaction (RT-PCR), and it is mostly cytoplasmic. The tracking of the subcellular localization of Ngn3 in neurons infected with a virus expressing myc-Ngn3 suggests that the protein is quickly translocated to the cell nucleus after synthesis and then reexported to the cytoplasm. Treatment with leptomycinB, a potent and specific inhibitor of the exportin CRM1, induced its accumulation into the nucleus, suggesting that CRM1 mediates the nuclear export of Ngn3. These results suggest that Ngn3 may play a role in neuronal development by actions in the cytoplasm. J. Comp. Neurol. 518: 1814-1824, 2010. (C) 2009 Wiley-Liss, Inc.