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神经发育过程中的基因表达调控机制以及相关的神经发育性疾病

丁保金^*

马萨诸塞大学医学院神经生物系，伍斯特市 01655，美国

摘要

在中枢神经系统的发育过程中，内在的基因和外在的环境因素相互作用以确保神经元发育的各个阶段(如神经细胞的增殖、分化、迁移，轴突延伸，树突成长，功能性突触的形成等)有序进行。这一过程需要众多的基因表达调控机制对不同基因的表达水平进行精确的时空调节。这些调控机制包括了序列特异性DNA结合蛋白(转录因子等)、组蛋白修饰、DNA甲基化、以及微小RNA (miRNA)等。它们形成了一个调控网络，在神经发育的不同阶段以及不同的环境刺激因素的情况下，从染色质的结构、基因的转录和蛋白质的翻译等不同层次上实现基因表达的精确调控。神经元发育过程中基因表达失调与一些神经发育性疾病相关，例如自闭症谱系障碍，Rett综合征，脆性X综合征以及其他遗传性疾病。深入研究神经元发育过程中基因表达调控机制可望能够给这些神经发育性疾病的诊断和治疗提供新的思路。

关键词： 神经发育; 基因表达; 调控机制; 转录; 表观遗传学; 组蛋白修饰; DNA甲基化; 神经发育障碍; 自闭症谱系障碍

分类号：R338；Q7

Gene expression in maturing neurons: regulatory mechanisms and related neurodevelopmental disorders

DING Baojin^*

Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01655, USA

Abstract

During the central nervous system (CNS) development, the interactions between intrinsic genes and extrinsic environment ensure that each neuronal developmental stage (eg. neuronal proliferation, differentiation, migration, axon extension, dendritogenesis and formation of functional synapses) occurs in the proper timing and sequence. The successful coordination requires that numerous groups of genes are exquisitely regulated in a spatiotemporal manner by various regulatory mechanisms, including sequence-specific DNA-binding proteins, histone modifications, DNA methylation, chromatin remodeling, and microRNAs (miRNAs). By targeting chromatin structure, transcription and translation processes, these mechanisms form a regulatory network to accomplish the fine regulation of gene expression in response to environmental stimuli at different developmental stages. Dysregulation of the gene expression during neuronal development has been shown to be implicated in a number of neurodevelopmental disorders, such as autism spectrum disorders (ASD), Rett syndrome (RTT), Fragile-X syndrome (FXS) and other genetic diseases. The further understanding of the regulation of gene expression during neuronal development may provide new approaches for the diagnosis and treatment of these disorders.

Key words: neuronal development; gene expression; regulatory mechanisms; transcription; epigenetics; histone modification; DNA methylation; neurodevelopmental disorders; autism spectrum disorders

收稿日期：2014-09-20　　录用日期：2014-12-04

通讯作者：丁保金　　E-mail: Baojin.Ding@umassmed.edu

引用本文：

丁保金. 神经发育过程中的基因表达调控机制以及相关的神经发育性疾病[J]. 生理学报 2015; 67 (2): 113-133.

DING Baojin. Gene expression in maturing neurons: regulatory mechanisms and related neurodevelopmental disorders. Acta Physiol Sin 2015; 67 (2): 113-133 (in Chinese with English abstract).