Optogenetic Rescue of a Patterning Mutant.
Optogenetic Rescue of a Patterning Mutant.
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DOI：
10.1016/j.cub.2020.06.059
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发表时间：
2020-09-07
期刊：
影响因子：
--
通讯作者：
Toettcher JE
中科院分区：
文献类型：
--
作者：
Johnson HE;Djabrayan NJV;Shvartsman SY;Toettcher JE
动物胚胎是由几个高度保守的感应信号构成的。然而，在大多数情况下，不知道需要哪种模式特征(即，空间梯度或时间动力学)来支持正常发育。解决这个问题的理想实验是在“空白的画布”胚胎上“描绘”任意的合成信号模式，以剖析它们的需求。在这里，我们通过结合光遗传控制的RAS/Erk信号和早期果蝇胚胎中受体酪氨酸激酶驱动的末端信号模式的遗传丢失来确切地展示这种能力。在胚胎末端进行90分钟的蓝光照射足以挽救正常发育，从一个否则致命的末端信号突变体中产生可存活的幼虫和可育的成虫。即使使用一种简单的、全有或全无的光输入来降低ERK活性的梯度并消除末端GAP基因表达的时空差异，光遗传拯救也是可能的。系统地改变光照参数进一步揭示了至少三个不同的发育程序在不同的信号阈值下被触发，并且原肠形成的形态发生运动对后部图案宽度的三倍变化是健壮的。这些结果为用简单的光学刺激控制组织打开了大门，提供了新的工具来探索自然发育过程，创造具有特定组织的合成组织，或直接纠正导致发育缺陷的图案化错误。
Animal embryos are patterned by a handful of highly conserved inductive signals. Yet in most cases it is unknown which pattern features (i.e., spatial gradients or temporal dynamics) are required to support normal development. An ideal experiment to address this question would be to “paint” arbitrary synthetic signaling patterns on “blank canvas” embryos to dissect their requirements. Here we demonstrate exactly this capability by combining optogenetic control of Ras/Erk signaling with the genetic loss of the receptor tyrosine kinase-driven terminal signaling patterning in early Drosophila embryos. Blue light illumination at the embryonic termini for 90 min was sufficient to rescue normal development, generating viable larvae and fertile adults from an otherwise-lethal terminal signaling mutant. Optogenetic rescue was possible even using a simple, all-or-none light input that reduced the gradient of Erk activity and eliminated spatiotemporal differences in terminal gap gene expression. Systematically varying illumination parameters further revealed that at least three distinct developmental programs are triggered at different signaling thresholds, and that the morphogenetic movements of gastrulation are robust to a three-fold variation in the posterior pattern width. These results open the door to controlling tissue organization with simple optical stimuli, providing new tools to probe natural developmental processes, create synthetic tissues with defined organization, or directly correct the patterning errors that underlie developmental defects.
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