Systems biology of facial development: contributions of ectoderm and mesenchyme.

Systems biology of facial development: contributions of ectoderm and mesenchyme.
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DOI:
10.1016/j.ydbio.2017.03.025
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发表时间:
2017-06-01
影响因子:
2.7
通讯作者:
Williams T
Williams T
中科院分区:
生物学3区
文献类型:
--
作者:
Hooper JE;Feng W;Li H;Leach SM;Phang T;Siska C;Jones KL;Spritz RA;Hunter LE;Williams T

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以基因为中心的生物学知识的快速增长,加上全基因组数据整合的分析方法,为发展对面部发育的系统级理解提供了机会。实验分析已经证明了表面外胚层和底层间充质之间的信号在协调面部图案中的重要性。然而,目前发育中脊椎动物面部的转录组数据主要是由间充质成分,外胚层的贡献不容易确定。我们已经从小鼠面部形成的关键时期生成了转录组数据集,这些数据集使基因表达能够根据时间,突出和组织层进行分析。值得注意的是,通过分离外胚层和间充质,我们大大提高了灵敏度相比,从全基因组获得的数据,在更宽的动态范围内检测到更多的基因。从这些数据中,我们生成了外胚层特异性发育程序的详细描述,包括泛外胚层程序、突出特异性程序及其时间动态。这些程序中的基因和途径为外胚层发育的几个方面提供了机制性的见解。我们还使用这些数据来识别特定于面部发育的共表达模块。然后,我们使用了14个共表达模块丰富的基因参与口面裂,使特定的机制预测基因参与舌规范,鼻突图案和颌骨发育。我们的多维基因表达数据集是一个独特的资源,系统分析的发展中的脸;我们的共表达模块是一个资源,用于预测功能差注释的基因,或预测的作用,尚未被研究的基因在面部发育的背景下;和我们的分析方法提供了一个范例,分析其他复杂的发展计划。
The rapid increase in gene-centric biological knowledge coupled with analytic approaches for genomewide data integration provides an opportunity to develop systems-level understanding of facial development. Experimental analyses have demonstrated the importance of signaling between the surface ectoderm and the underlying mesenchyme in coordinating facial patterning. However, current transcriptome data from the developing vertebrate face is dominated by the mesenchymal component, and the contributions of the ectoderm are not easily identified. We have generated transcriptome datasets from critical periods of mouse face formation that enable gene expression to be analyzed with respect to time, prominence, and tissue layer. Notably, by separating the ectoderm and mesenchyme we considerably improved the sensitivity compared to data obtained from whole prominences, with more genes detected over a wider dynamic range. From these data we generated a detailed description of ectoderm-specific developmental programs, including pan-ectodermal programs, prominence- specific programs and their temporal dynamics. The genes and pathways represented in these programs provide mechanistic insights into several aspects of ectodermal development. We also used these data to identify co-expression modules specific to facial development. We then used 14 co-expression modules enriched for genes involved in orofacial clefts to make specific mechanistic predictions about genes involved in tongue specification, in nasal process patterning and in jaw development. Our multidimensional gene expression dataset is a unique resource for systems analysis of the developing face; our co-expression modules are a resource for predicting functions of poorly annotated genes, or for predicting roles for genes that have yet to be studied in the context of facial development; and our analytic approaches provide a paradigm for analysis of other complex developmental programs.
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