中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (20): 1863-1871.doi: 10.3969/j.issn.1673-5374.2013.20.005

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

细胞周期相关基因p57kip2、Cdk5和 Spin在神经管发育缺陷发生过程中的作用

  

  • 收稿日期:2012-06-07 修回日期:2012-09-19 出版日期:2013-07-15 发布日期:2013-07-15

Cell cycle-related genes p57kip2, Cdk5 and Spin in the pathogenesis of neural tube defects

Xinjun Li1, Zhong Yang2, Yi Zeng3, Hong Xu1, Hongli Li2, Yangyun Han1, Xiaodong Long1, Chao You4   

  1. 1 Department of Neurosurgery, Deyang People’s Hospital, Deyang 618000, Sichuan Province, China
    2 Department of Neurobiology, the Third Military Medical University of Chinese PLA, Chongqing 400038, China
    3 Department of Neurosurgery, Sichuan Provincial People’s Hospital, Chengdu 610041, Sichuan Province, China
    4 Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2012-06-07 Revised:2012-09-19 Online:2013-07-15 Published:2013-07-15
  • Contact: Hong Xu, Master, Chief physician, Department of Neurosurgery, Deyang People’s Hospital, Deyang 618000, Sichuan Province, China, jy988lxj @sina.com.
  • About author:Xinjun Li, Master, Attending physician.

摘要:

发育神经生物学学者认为神经管形成过程中准确有序的细胞周期调控和细胞凋亡是保证神经管正常发生的2个重要因素。课题组在前期实验中发现多个基因参与了神经管发育缺陷过程。实验设计一次性喂服孕鼠维甲酸制备神经管发育缺陷模型。通过基因芯片杂交分析发现细胞周期与凋亡相关基因、信号转导基因、转录与翻译调控、能量与代谢基因、热休克基因、基质与骨架蛋白等多种种类基因参与神经管发育缺陷的形成。其中细胞周期相关基因所占比例最大。实验同时发现在维甲酸处理后,有3个细胞周期相关基因出现差异表达,在维甲酸作用后呈现下调趋势,而在正常神经管形成时呈上调,这3个基因分别为 p57kip2,Cdk5和 Spin。结果提示细胞周期相关基因可能在神经管缺陷发生的过程中发挥重要作用。p57kip2、Cdk5、Spin三个基因可能是参与神经管缺陷发生的关键基因。

关键词: 神经管缺陷, 神经胚形成, 基因芯片, 细胞周期, 维甲酸, 调控因子, 神经发育, 再生, 神经再生

Abstract:

In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cell cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were all involved in the formation of developmental neural tube defects. Among these, cell cycle-related genes were predominant. Retinoic acid treat-ment caused differential expression of three cell cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cell cycle-related genes play an im-portant role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.