Johnson Heath E, Goyal Yogesh, Pannucci Nicole L, Schüpbach Trudi, Shvartsman Stanislav Y, Toettcher Jared E
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Dev Cell. 2017 Jan 23;40(2):185-192. doi: 10.1016/j.devcel.2016.12.002.
Animal development is characterized by signaling events that occur at precise locations and times within the embryo, but determining when and where such precision is needed for proper embryogenesis has been a long-standing challenge. Here we address this question for extracellular signal regulated kinase (Erk) signaling, a key developmental patterning cue. We describe an optogenetic system for activating Erk with high spatiotemporal precision in vivo. Implementing this system in Drosophila, we find that embryogenesis is remarkably robust to ectopic Erk signaling, except from 1 to 4 hr post-fertilization, when perturbing the spatial extent of Erk pathway activation leads to dramatic disruptions of patterning and morphogenesis. Later in development, the effects of ectopic signaling are buffered, at least in part, by combinatorial mechanisms. Our approach can be used to systematically probe the differential contributions of the Ras/Erk pathway and concurrent signals, leading to a more quantitative understanding of developmental signaling.
动物发育的特征是在胚胎内精确的位置和时间发生信号传导事件，但确定在何时何地这种精确性对于正常胚胎发生是必需的，一直是一项长期挑战。在这里，我们针对细胞外信号调节激酶（Erk）信号传导（一种关键的发育模式线索）来解决这个问题。我们描述了一种在体内以高时空精度激活Erk的光遗传学系统。在果蝇中实施这个系统时，我们发现胚胎发生对异位Erk信号传导具有显著的稳健性，除了在受精后1至4小时，此时扰乱Erk信号通路激活的空间范围会导致模式形成和形态发生的剧烈破坏。在发育后期，异位信号传导的影响至少部分地通过组合机制得到缓冲。我们的方法可用于系统地探究Ras/Erk信号通路和并发信号的不同贡献，从而对发育信号传导有更定量的理解。
