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CXCR4在小脑颗粒神经元发育过程中的作用

发表时间:2018-12-14  浏览量:1531  下载量:153
全部作者: 胡建,程艳,王媛
作者单位: 苏州大学药学院
摘 要: 目的:研究趋化因子受体CXCR4对小脑发育过程中颗粒神经元前体细胞(granule neuron precursors,GNPs)增殖与迁移的影响。方法:使用条件性基因敲除小鼠(Math1-Cre/CXCR4flox/flox)及分子生物学技术检测CXCR4 在小脑发育过程中的表达以及对颗粒神经元发育的影响。结果:1)小鼠小脑的CXCR4在产后第4天(P4)表达最高,随着小脑的发育其表达逐渐下降;2)CXCR4 的缺失造成部分GNPs群过早地迁移至内颗粒层(inner granule layer,IGL),并且这些异位的细胞仍然保持增殖能力;3)CXCR4的敲低造成Shh信号通路相关靶基因表达水平的下调,但是并不影响GNPs和髓母细胞瘤(medulloblastoma,MB)细胞的正常增殖能力。结论:CXCR4介导的信号传导可以防止发育过程中GNPs过早地从外颗粒层(external germinal layer,EGL)迁移,从而维持颗粒神经元增殖、迁移和分化的协调进行。
关 键 词: 药理学;趋化因子;CXCR4;小脑发育;颗粒神经元前体细胞
Title: Function of CXCR4 in the development of cerebellar granule neuron
Author: HU Jian, CHENG Yan, WANG Yuan
Organization: College of Pharmaceutical Sciences, Soochow University
Abstract: Objective: To investigate the effect of chemokine receptor CXCR4 on the proliferation and migration of granule neuron precursors (GNPs) during cerebellar development. Methods: Conditional knockout mice (Math1-Cre/CXCR4flox/flox) and molecular biology technigues were used to detect the expression of CXCR4 in cerebellar development and its effects on granular neuron development. Results: 1) The expression of CXCR4 in mice cerebellum is the highest on postnatal day 4 (P4), then gradually decreases with the development of the cerebellum. 2) Deletion of CXCR4 in cerebellum causes premature migration of a population of GNPs to inner granule layer (IGL), throughout development that are capable of proliferation outside of their normal mitogenic niche. 3) Knockdown of CXCR4 causes a reduction in the activation of Sonic hedgehog (Shh) signaling pathway, but exerts normal proliferation in GNPs and medulloblastoma (MB) cells. Conclusion: CXCR4-mediated signaling transduction prevents GNPs premature migration from external germinal layer (EGL) during development, thereby maintaining coordination of proliferation, migration and differentiation in granule neuron.
Key words: pharmacology; chemokines; CXCR4; cerebellar development; granule neuron precursors
发表期数: 2018年12月第23期
引用格式: 胡建,程艳,王媛. CXCR4在小脑颗粒神经元发育过程中的作用[J]. 中国科技论文在线精品论文,2018,11(23):2383-2389.
 
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