Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation.
Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation.
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DOI：
10.1016/j.celrep.2022.110543
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发表时间：
2022-03-22
期刊：
影响因子：
8.8
通讯作者：
Toettcher, Jared E.
中科院分区：
文献类型：
--
作者：
Singh, Anand P.;Wu, Ping;Ryabichko, Sergey;Raimundo, Joao;Swan, Michael;Wieschaus, Eric;Gregor, Thomas;Toettcher, Jared E.
发育模式网络受到多个输入和反馈连接的调节，这些输入和反馈连接迅速重塑基因表达，限制了只能从缓慢的遗传扰动中获得的信息。在这里，我们表明，快速光遗传学刺激，实时转录报告，和一个简化的遗传背景可以结合起来，揭示在体内的发育转录因子的基因表达的动力学下游。我们设计了Bicoid转录因子的光控版本，并研究了它们对胚胎中下游gap基因的影响。我们的研究结果概括了已知的关系，包括快速Bicoid依赖的转录巨人和驼背和延迟镇压Krüppel。此外，我们发现，后模式的knirps表现出快速，但反向响应Bicoid扰动，这表明一个noncanonical的作用Bicoid直接抑制knirps转录。在记录输出基因活性的同时对转录因子浓度进行急性调节是研究体内发育基因网络的有力方法。Singh等人研究了核Bicoid水平的快速变化如何动态调节其靶基因的表达。结合光遗传学刺激和简化的遗传背景，他们的结果概括了Bicoid作为转录激活因子的经典作用，并揭示了直接kni抑制中可能的非经典作用。
Developmental patterning networks are regulated by multiple inputs and feedback connections that rapidly reshape gene expression, limiting the information that can be gained solely from slow genetic perturbations. Here we show that fast optogenetic stimuli, real-time transcriptional reporters, and a simplified genetic background can be combined to reveal the kinetics of gene expression downstream of a developmental transcription factor in vivo. We engineer light-controlled versions of the Bicoid transcription factor and study their effects on downstream gap genes in embryos. Our results recapitulate known relationships, including rapid Bicoid-dependent transcription of giant and hunchback and delayed repression of Krüppel. In addition, we find that the posterior pattern of knirps exhibits a quick but inverted response to Bicoid perturbation, suggesting a noncanonical role for Bicoid in directly suppressing knirps transcription. Acute modulation of transcription factor concentration while recording output gene activity represents a powerful approach for studying developmental gene networks in vivo. Singh et al. investigate how rapid changes in nuclear Bicoid levels dynamically regulate expression of its target genes. Combining optogenetic stimulation and a simplified genetic background, their results recapitulate the canonical role of Bicoid as a transcriptional activator and reveal a possible noncanonical role in direct kni repression.
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影响因子：
2.6
作者：
Gavis, Elizabeth R.;Chatterjee, Seema;Wolff, Lisa J.
通讯作者：
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影响因子：
64.8
作者：
HULSKAMP, M;PFEIFLE, C;TAUTZ, D
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DOI：
10.1016/j.cub.2016.02.054
发表时间：
2016-05-09
期刊：
Current biology : CB
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Rincon-Limas DE