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A gene expression atlas of a bicoid-depleted Drosophila embryo reveals early canalization of cell fate

机译:二倍体耗尽果蝇胚胎的基因表达图谱揭示了细胞命运的早期渠道化

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摘要

In developing embryos, gene regulatory networks drive cells towards discrete terminal fates, a process called canalization. We studied the behavior of the anterior-posterior segmentation network in Drosophila melanogaster embryos by depleting a key maternal input, bicoid (bcd), and measuring gene expression patterns of the network at cellular resolution. This method results in a gene expression atlas containing the levels of mRNA or protein expression of 13 core patterning genes over six time points for every cell of the blastoderm embryo. This is the first cellular resolution dataset of a genetically perturbed Drosophila embryo that captures all cells in 3D. We describe the technical developments required to build this atlas and how the method can be employed and extended by others. We also analyze this novel dataset to characterize the degree and timing of cell fate canalization in the segmentation network. We find that in two layers of this gene regulatory network, following depletion of bcd, individual cells rapidly canalize towards normal cell fates. This result supports the hypothesis that the segmentation network directly canalizes cell fate, rather than an alternative hypothesis whereby cells are initially mis-specified and later eliminated by apoptosis. Our gene expression atlas provides a high resolution picture of a classic perturbation and will enable further computational modeling of canalization and gene regulation in this transcriptional network.
机译:在发育中的胚胎中,基因调控网络驱动细胞朝着离散的最终命运发展,这一过程被称为渠道化。我们研究了果蝇黑腹果蝇胚胎中前-后分割网络的行为,方法是耗尽关键的母亲输入(双曲线)(bcd),并在细胞分辨率下测量网络的基因表达模式。这种方法产生的基因表达图谱包含了胚盘每个细胞六个时间点的13个核心模式基因的mRNA或蛋白质表达水平。这是遗传扰动的果蝇胚胎的第一个细胞分辨率数据集,可捕获3D的所有细胞。我们描述了构建此地图集所需的技术发展,以及其他人如何采用和扩展该方法。我们还分析了这个新颖的数据集,以表征分割网络中细胞命运渠化的程度和时机。我们发现,在该基因调控网络的两层中,bcd耗尽后,单个细胞迅速向正常细胞命运转移。该结果支持以下假设:分割网络直接影响了细胞命运,而不是另一种假设,即细胞最初被错误指定,随后被凋亡清除。我们的基因表达图谱提供了经典扰动的高分辨率图片,并将使该转录网络中的渠道化和基因调控能够进行进一步的计算建模。

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