A rationally designed optochemogenetic switch for activating canonical Wnt signaling

• Published in: iScience 2023-03, Vol.26 (3), p.106233-106233, Article 106233
• Main Authors: Lee, Seunghwan, Cui, Mingguang, Lee, Donghun, Han, Kihoon, Sun, Woong, Lee, Dongmin
• Format: Article
• Language: English
• Subjects: Biochemistry methods; Functional aspects of cell biology; Methodology in biological sciences
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106233

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. [Display omitted] •We developed a genetically encoded Wnt activator termed optochemoWnt•OptochemoWnt is optochemogenetically triggered by AND logic gating•The dual-triggered switch reduces signal leakage and enables precise spatial control Biochemistry methods; Functional aspects of cell biology; Methodology in biological sciences