Huang Anqi, Amourda Christopher, Zhang Shaobo, Tolwinski Nicholas S, Saunders Timothy E
Mechanobiology Institute, National University of Singapore, Singapore, Singapore.
Division of Science, Yale-NUS College, Singapore, Singapore.
Elife. 2017 Jul 10;6:e26258. doi: 10.7554/eLife.26258.
Morphogen gradients provide essential spatial information during development. Not only the local concentration but also duration of morphogen exposure is critical for correct cell fate decisions. Yet, how and when cells temporally integrate signals from a morphogen remains unclear. Here, we use optogenetic manipulation to switch off Bicoid-dependent transcription in the early embryo with high temporal resolution, allowing time-specific and reversible manipulation of morphogen signalling. We find that Bicoid transcriptional activity is dispensable for embryonic viability in the first hour after fertilization, but persistently required throughout the rest of the blastoderm stage. Short interruptions of Bicoid activity alter the most anterior cell fate decisions, while prolonged inactivation expands patterning defects from anterior to posterior. Such anterior susceptibility correlates with high reliance of anterior gap gene expression on Bicoid. Therefore, cell fates exposed to higher Bicoid concentration require input for longer duration, demonstrating a previously unknown aspect of Bicoid decoding.
形态发生素梯度在发育过程中提供重要的空间信息。不仅形态发生素的局部浓度，而且其暴露的持续时间对于正确的细胞命运决定都至关重要。然而，细胞如何以及何时在时间上整合来自形态发生素的信号仍不清楚。在这里，我们使用光遗传学操作以高时间分辨率在早期胚胎中关闭依赖于双尾的转录，从而实现对形态发生素信号的时间特异性和可逆性操作。我们发现，双尾转录活性在受精后的第一个小时对于胚胎存活是可有可无的，但在胚盘阶段的其余时间一直是必需的。双尾活性的短暂中断会改变最前端的细胞命运决定，而长时间失活则会使模式缺陷从前向后扩展。这种前端易感性与前端间隙基因表达对双尾的高度依赖相关。因此，暴露于较高双尾浓度的细胞命运需要更长时间的输入，这揭示了双尾解码一个以前未知的方面。
