Lee Seunghwan, Cui Mingguang, Lee Donghun, Han Kihoon, Sun Woong, Lee Dongmin
Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea.
iScience. 2023 Feb 19;26(3):106233. doi: 10.1016/j.isci.2023.106233. eCollection 2023 Mar 17.
Accurate spatiotemporal control of multicellular self-organization by various signaling pathways is essential for developmental stages. In particular, evolutionarily conserved Wnt signaling serves as a major morphogenetic switch to determine the anteroposterior axis of the embryo. Here, we developed a genetically encoded optochemogenetic Wnt switch, named optochemoWnt, by coupling a blue light-inducible CRY2olig and rapamycin-inducible LRP6c clustering. The rationally designed optochemoWnt successfully modulated Wnt signaling with AND-gated patterns and demonstrated an improved signal-to-noise ratio (SNR). The dual-triggered switch provides a safeguard to prevent signal leakage resulting from ambient light sources under general laboratory conditions. OptochemoWnt expands the molecular toolbox available for the fields of developmental biology and tissue engineering. In addition, the AND-gated strategy of optochemoWnt may be used for other biomedical applications that integrate user defined switch elements with Boolean logic gates.
通过各种信号通路对多细胞自组织进行精确的时空控制对于发育阶段至关重要。特别是，进化上保守的Wnt信号作为主要的形态发生开关，决定胚胎的前后轴。在这里，我们通过将蓝光诱导的CRY2olig和雷帕霉素诱导的LRP6c聚集相结合，开发了一种基因编码的光化学遗传学Wnt开关，命名为optochemoWnt。合理设计的optochemoWnt成功地以与门模式调节Wnt信号，并显示出改善的信噪比（SNR）。这种双触发开关提供了一种保障，以防止在一般实验室条件下由环境光源导致的信号泄漏。OptochemoWnt扩展了可用于发育生物学和组织工程领域的分子工具箱。此外，optochemoWnt的与门策略可用于其他生物医学应用，即将用户定义的开关元件与布尔逻辑门集成。
