Shared molecular networks in orofacial and neural tube development.
Shared molecular networks in orofacial and neural tube development.
复制标题
口面部和神经管发育中的共享分子网络。
DOI：
10.1002/bdra.23598
复制
发表时间：
2017
影响因子：
2.1
通讯作者：
Schutte,BrianC
中科院分区：
文献类型：
--
作者：
Kousa,YoussefA;Mansour,TamerA;Seada,Haitham;Matoo,Samaneh;Schutte,BrianC
背景：在发育过程中，单个基因变异可以影响多个组织。因此，共享基因调控网络的破坏可能是综合征表现的基础。在这项研究中，我们通过检查控制口面部和神经管发育的两个关键发育程序来探索这一观点，并确定了共同的调节因素和网络。这些网络的识别有可能为尚不清楚的发育障碍提供额外的候选基因，并有助于建模和管理风险因素，以预防发病和死亡。方法回顾文献，寻找口面部和神经管缺陷与发育的共同基因。然后，我们进行了生物信息学分析，以确定这些组织发育中的共同分子靶点和途径。最后，我们检查了公开可用的RNA - Seq数据，以确定在发育过程中这些基因中哪些在两种组织中表达。结果我们发现了口面部和神经管发育的共同调节因子。通路富集分析表明，叶酸、癌症和刺猬信号通路在神经管和口面部发育中是共享的。发育中的神经组织差异表达小鼠外脑畸形和腭裂基因，而发育中的口面组织则丰富表达小鼠腭裂和神经管缺陷基因。结论颅面缺损与神经管缺损具有共同的关键发育因素和通路。我们的结论是，关注共同的调节因素和途径，以更好地了解这些出生缺陷的病理和制定预防措施，可能是最有益的。出生缺陷研究[j]， 2017。©2016 Wiley期刊公司
BackgroundSingle genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks. Identification of these networks has the potential to yield additional candidate genes for poorly understood developmental disorders and assist in modeling and perhaps managing risk factors to prevent morbidly and mortality.MethodsWe reviewed the literature to identify genes common between orofacial and neural tube defects and development. We then conducted a bioinformatic analysis to identify shared molecular targets and pathways in the development of these tissues. Finally, we examine publicly available RNA‐Seq data to identify which of these genes are expressed in both tissues during development.ResultsWe identify common regulatory factors in orofacial and neural tube development. Pathway enrichment analysis shows that folate, cancer and hedgehog signaling pathways are shared in neural tube and orofacial development. Developing neural tissues differentially express mouse exencephaly and cleft palate genes, whereas developing orofacial tissues were enriched for both clefting and neural tube defect genes.ConclusionThese data suggest that key developmental factors and pathways are shared between orofacial and neural tube defects. We conclude that it might be most beneficial to focus on common regulatory factors and pathways to better understand pathology and develop preventative measures for these birth defects. Birth Defects Research 109:169–179, 2017. © 2016 Wiley Periodicals, Inc.