The molecular regulatory networks involved in the neural crest cell development: a bioinformatic analysis

doi:10.3969/j.issn.2095-4344.2016.24.019

Abstract

Abstract:

BACKGROUND: Development of neural crest cells, which is regulated by various genes, plays an important role in the formation of central nervous system, heart, craniofacial organs and other tissues. However, the relationship among these genes is unclear.
OBJECTIVE: To investigate the molecular regulatory networks involved in the process of neural crest cell development based on a bioinformatic analysis.
METHODS: Totally 500 differentially expressed genes during the process of neural crest cell development were obtained from the GEO on-line database. Then the DAVID and STRING on-line databases were used to evaluate the relationship among these genes.
RESULTS AND CONCLUSION: Totally 500 differentially expressed genes during the process of neural crest cell development could be enriched into different subgroups based on the analysis of DAVID database, including “transforming growth factor β signal pathway”, “WNT signal pathway”, “homeobox gene” , “neural crest cell differentiation” and “neural tube development”. Additionally, 12 genes molecular networks were built based on the analysis of STRING database, such as DLX5, MSX2, SNAIL2, PAX7, SHH, SOX9, NOG, GSC, KAL1, bone morphogenetic protein 5, fibroblast growth factor 8 and WNT3a .These genes exhibited interactions by co-expression, activation and antagonism. Therefore, many genes involved in the process of neural crest cell development were interacted and formed the networks. These findings imply that we should understand these neural crest-related diseases from a holistic view of the signaling pathway and molecular regulatory networks.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Gene Regulatory Network, Signal Transducing, Computational Biology

CLC Number:

R318

Wang Jun-fang, Wang Jia-qi, Bi Qing-wei, Yin Han-wen, Zhang Guo-liang. The molecular regulatory networks involved in the neural crest cell development: a bioinformatic analysis[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(24): 3621-3627.

Figures/Tables 3

2.1 神经嵴细胞发生时差异表达的基因被富集在不同的“信号通路”、“分子功能”和“生物学过程”子集从GEO Datasets数据库获取了神经嵴细胞发生时差异表达的500个基因，这些基因之间的关系并不清楚。本研究中应用DAVID在线数据库对这500个基因进行生物信息学分析，结果显示这些基因可以富集到不同的“信号通路”、“分子功能”和“生物学过程”子集中。在信号通路子集中，按照KEGG数据库的分类，这500个基因中部分基因被富集到了10个不同的子集(表1)，其中SMAD6、骨形态发生蛋白5、PITX2和TGFB2等10个基因属于转化生长因子β信号通路，这10个基因在整个转化生长因子β信号通路所处的位置及与其他信号通路的关系如图1所示。此外，NKD1、SOX17、AXIN2和WNT6等8个基因富集在WNT信号通路，GLG1、NCAM1、ITGA6和NLGN1等8个基因富集在细胞黏附分子信号通路。这些信号通路都与神经嵴发育密切相关。按照“功能关键词”进行分类，这500个基因中部分基因被富集到了多个不同的分子功能子集，其中与神经嵴发育密切相关的子集见表2，包括同源盒基因、生长因子、黏附因子和细胞外基质等。同源盒基因中包括GSC、OTX2、PAX3、MSX2、DLX6、PITX2等14个基因，已有研究表明这些基因对神经嵴细胞的发育具有十分重要的调控作用。按照GO数据库的“生物学过程”进行分类，这500个基因中部分基因可被富集到了多个不同的生物学过程子集(表3)，包括胚胎形态发生、神经嵴细胞分化、神经嵴细胞迁移、神经管发育和骨骼系统发育等。其中神经嵴细胞分化子集包括成纤维细胞生长因子19、PAX3、SOX9和 SHH等8个基因，神经管发育子集包括GSC、PAX7、SHH和TWIST1等9个基因。这些对神经嵴细胞的发育具有十分重要的调控作用的基因按照一定的规律都进行了分类。 2.2 神经嵴细胞发生关键调控基因的分子网络应用STRING数据库分析DLX5、MSX2、SNAIL2、PAX7、SHH、SOX9、NOG、GSC、KAL1、骨形态发生蛋白5、成纤维细胞生长因子8和WNT3a等12个基因之间关系，结果显示这些基因之间存在相互作用的分子网络。STRING可以“Actions”、“Evidence”和“Interactive”等模式显示这些基因的分子网络图。当以“Actions”显"

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