遗传 ›› 2013, Vol. 35 ›› Issue (10): 1198-1208.doi: 10.3724/SP.J.1005.2013.01198

• 研究报告 • 上一篇    下一篇

小鼠内耳发育核心转录因子的保守性及调控网络的比较分析

陈志强1, 韩新焕2, 魏钦俊2, 邢光前1, 曹新2   

  1. 1. 南京医科大学第一临床医学院, 南京 210029; 
    2. 南京医科大学基础医学院, 南京 210029
  • 收稿日期:2013-04-22 修回日期:2013-07-21 出版日期:2013-10-20 发布日期:2013-10-25
  • 通讯作者: 韩新焕, 副教授, 研究方向:数学与计算机应用。 E-mail:hxinhuan@163.com
  • 作者简介:陈志强, 本硕连读生, 专业方向:临床医学。E-mail: erwin_0108@sina.com
  • 基金资助:

    国家级大学生创新创业训练计划项目(编号:201210312014), 江苏省高等学校大学生实践创新训练计划项目(重点)(编号:2012JSSPITP1045)和江苏高校优势学科建设工程项目资助

Comparative analysis of conservation and regulatory network on core transcription factors in mouse inner ear development

CHEN Zhi-Qiang1, HAN Xin-Huan2, WEI Qin-Jun2, XING Guang-Qian1, CAO Xin2   

  1. 1. The First Clinical Medical College, Nanjing Medical University, Nanjing 210029, China; 
    2. School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China
  • Received:2013-04-22 Revised:2013-07-21 Online:2013-10-20 Published:2013-10-25

摘要:

在脊椎动物内耳发育中, Six1、Six4、Pax2、Pax8、Foxi1、Dlx5、Gbx2、Irx2/3、Msx1等基因作为核心调控基因参与听基板的诱导过程。文章通过生物信息学方法, 对小鼠内耳发育的核心转录因子进行保守性分析并研究其相互调控关系, 得到小鼠内耳发育过程中核心转录因子的基因调控网络。与文献中已知的小鼠内耳发育基因调控关系相比, Pax2、Pax8、Foxi1、Dlx5基因在内耳发育中仍然起主要调控者的角色, Six1则处于被多个转录因子调节的地位, Gbx2、Irx2/3、Msx1在调控网络中也起到重要作用。对出现的差异进行了合理的分析, 同时结合构建的调控网络预测了可能存在的Msx1对Six1、Gbx2的调控作用。序列预测结果也发现了一些新的调控关系, 所涉及的转录因子包括Sox5、Lhx2、Rax、Otx1、Otx2、Pitx1、Pitx2、Nkx2-5、Irx4、Irx6、Dlx2、Hmx1/2/3、Pou4f3、Pax4、Tlx2。文章为深入了解内耳发育调控机制提供了基础信息。

关键词: 内耳发育, 转录因子, 调控网络

Abstract:

During vertebrate inner ear development, several core genes, such as Six1, Six4, Pax2, Pax8, Foxi1, Dlx5, Gbx2, Irx2/3, and Msx1, are crucial to the regulation of the otic placode induction. In order to get the gene regulatory network during inner ear development, bioinformatics methods were adopted to analyze conservation and regulation of the core transcription factors in mice. Pax2, Pax8, Foxi1, and Dlx5 remained to be the main regulators during inner ear development, which was consistent with the gene regulatory network from literature. Six1 was regulated by many transcription factors, and Gbx2, Irx2/3, and Msx1 played important roles in the regulatory network. The differences in the constructed regulatory network were reasonably analyzed. It was predicted that Msx1 regulated the expression of Six1 and Gbx2. In addition, several transcription factors, such as Sox5, Lhx2, Rax, Otx1, Otx2, Pitx1, Pitx2, Nkx2-5, Irx4, Irx6, Dlx2, Hmx1/2/3, Pou4f3, Pax4 and Tlx2, were found to be involved in the regulatory network. Our results provide an improved understanding of the regu-latory mechanism during inner ear development.

Key words: inner ear development, transcription factors, regulation network