[WITHDRAWN] Overlapping Targets of Shh and Gata3 during Craniofacial Development.

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Abstract

The full text of this preprint has been withdrawn by the authors while they make corrections to the work. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.

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Shh和Gata3在颅面发育过程中的重叠靶点。
背景:先天性出生缺陷是导致婴儿死亡的主要原因之一。这些缺陷的表型变异是遗传和环境因素共同作用的结果。这方面的一个例子是通过Sonic hedgehog(Shh)途径由转录因子Gata3的突变引起的腭表型的调节。我们将斑马鱼暴露于亚再生剂量的Shh拮抗剂环胺,并将另一组暴露于环胺和gata3敲除。我们对这些斑马鱼进行了RNA-seq,以表征Shh和Gata3靶点的重叠。结果:我们检测了那些表达模式反映了失调加剧的生物学效应的基因。与单独的Gata3相比,这些基因没有受到亚再生剂量乙醇的显著失调,但受到Shh和Gata3的组合破坏的失调更大。利用基因-疾病关联发现,我们能够将该基因列表细化为11个已发表与类似gata3表型或颅面畸形的临床结果链接的基因。我们还使用加权基因共表达网络分析来鉴定与Shh和Gata3的共调控密切相关的基因模块。该模块富含与Wnt信号传导相关的基因。结论:我们发现了许多对环胺治疗有反应的差异表达基因,甚至在双重治疗中有更多差异表达基因。最值得注意的是,我们发现了一组基因,其表达谱反映了Shh/Gata3相互作用的生物学效应。通路分析表明Wnt信号在味觉发育中Gata3/Shh相互作用中的重要性。
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