Gene length may contribute to graded transcriptional responses in the Drosophila embryo
Gene length may contribute to graded transcriptional responses in the Drosophila embryo
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DOI：
10.1016/j.ydbio.2011.08.016
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发表时间：
2011-12-01
影响因子：
2.7
通讯作者：
Hwa, Terence
中科院分区：
文献类型：
--
作者：
McHale, Peter;Mizutani, Claudia M.;Hwa, Terence
发育生物学中的一个重要问题是，相对较浅的形态发生素梯度如何可靠地建立一系列不同的转录读出。目前的模型强调转录因子之间的相互作用，以不同的方式结合到靶基因的顺式作用序列。另一个最近的想法是，顺式作用的相互作用可能会放大预先存在的偏见或预模式，以建立强大的转录反应。在这项研究中，我们研究了一个这样的来源的前模式，即基因长度的可能贡献。我们开发了定量成像工具来测量基因表达水平的几个位点在一个时间在单细胞的基础上，并应用这些定量成像工具来解剖建立一个基因表达边界分离中胚层和神经外胚层在早期果蝇胚胎。首先，我们的特点是形成了一个短暂的腹背梯度的蜗牛（Sna）阻遏物，然后检查这个梯度和神经靶基因在中胚层的镇压之间的关系。我们发现，神经基因被压制在一个嵌套的模式内的一个区的中胚层邻接的神经外胚层，其中SNA水平分级。虽然有几个因素可能有助于瞬时分级响应的Sna梯度，我们的分析表明，基因长度可能发挥重要的，虽然短暂的，在建立这些不同的转录反应的作用。基因长度依赖性转录模式模型的一个预测是，共调节基因knirps（短基因）和knirps相关（长基因）应该在不同宽度的结构域中瞬时表达，我们通过实验证实了这一点。这些研究结果表明，基因长度可能有助于建立分级反应形态梯度提供瞬时prepatterns，随后放大和稳定的传统顺式调控相互作用。(C)2011 Elsevier Inc. All rights reserved.
An important question in developmental biology is how relatively shallow gradients of morphogens can reliably establish a series of distinct transcriptional readouts. Current models emphasize interactions between transcription factors binding in distinct modes to cis-acting sequences of target genes. Another recent idea is that the cis-acting interactions may amplify preexisting biases or prepatterns to establish robust transcriptional responses. In this study, we examine the possible contribution of one such source of prepattern, namely gene length. We developed quantitative imaging tools to measure gene expression levels for several loci at a time on a single-cell basis and applied these quantitative imaging tools to dissect the establishment of a gene expression border separating the mesoderm and neuroectoderm in the early Drosophila embryo. We first characterized the formation of a transient ventral-to-dorsal gradient of the Snail (Sna) repressor and then examined the relationship between this gradient and repression of neural target genes in the mesoderm. We found that neural genes are repressed in a nested pattern within a zone of the mesoderm abutting the neuroectoderm, where Sna levels are graded. While several factors may contribute to the transient graded response to the Sna gradient, our analysis suggests that gene length may play an important, albeit transient, role in establishing these distinct transcriptional responses. One prediction of the gene-length-dependent transcriptional patterning model is that the co-regulated genes knirps (a short gene) and knirps-related (a long gene) should be transiently expressed in domains of differing widths, which we confirmed experimentally. These findings suggest that gene length may contribute to establishing graded responses to morphogen gradients by providing transient prepatterns that are subsequently amplified and stabilized by traditional cis-regulatory interactions. (C) 2011 Elsevier Inc. All rights reserved.