A rationally designed optochemogenetic switch for activating canonical Wnt signaling

Summary: 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...

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Main Authors: Seunghwan Lee, Mingguang Cui, Donghun Lee, Kihoon Han, Woong Sun, Dongmin Lee
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223003103
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author Seunghwan Lee
Mingguang Cui
Donghun Lee
Kihoon Han
Woong Sun
Dongmin Lee
author_facet Seunghwan Lee
Mingguang Cui
Donghun Lee
Kihoon Han
Woong Sun
Dongmin Lee
author_sort Seunghwan Lee
collection DOAJ
description Summary: 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.
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spelling doaj.art-0f58cb7456ff437186ad0e08d4b67c922023-03-05T04:25:12ZengElsevieriScience2589-00422023-03-01263106233A rationally designed optochemogenetic switch for activating canonical Wnt signalingSeunghwan Lee0Mingguang Cui1Donghun Lee2Kihoon Han3Woong Sun4Dongmin Lee5Department 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 KoreaDepartment 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 KoreaDepartment of Physics, Korea University, Seoul, Republic of KoreaBK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea; Department of Neuroscience, Korea University College of Medicine, Seoul, Republic of KoreaDepartment 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 KoreaDepartment 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223003103Biochemistry methodsFunctional aspects of cell biologyMethodology in biological sciences
spellingShingle Seunghwan Lee
Mingguang Cui
Donghun Lee
Kihoon Han
Woong Sun
Dongmin Lee
A rationally designed optochemogenetic switch for activating canonical Wnt signaling
iScience
Biochemistry methods
Functional aspects of cell biology
Methodology in biological sciences
title A rationally designed optochemogenetic switch for activating canonical Wnt signaling
title_full A rationally designed optochemogenetic switch for activating canonical Wnt signaling
title_fullStr A rationally designed optochemogenetic switch for activating canonical Wnt signaling
title_full_unstemmed A rationally designed optochemogenetic switch for activating canonical Wnt signaling
title_short A rationally designed optochemogenetic switch for activating canonical Wnt signaling
title_sort rationally designed optochemogenetic switch for activating canonical wnt signaling
topic Biochemistry methods
Functional aspects of cell biology
Methodology in biological sciences
url http://www.sciencedirect.com/science/article/pii/S2589004223003103
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