A rationally designed optochemogenetic switch for activating canonical Wnt signaling

Seunghwan Lee, Mingguang Cui, Donghun Lee, Kihoon Han, Woong Sun, Dongmin Lee

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number106233
JournaliScience
Volume26
Issue number3
DOIs
Publication statusPublished - 2023 Mar 17

Bibliographical note

Funding Information:
This study was supported by National Research Foundation of Korea (NRF) grants; the Korea Government Ministry of Science and Information and Communications Technology (ICT) ( NRF-2017M3A9B3085979 , NRF-2018M3C7A1024597 , and NRF-2020R1C1C1014793 to D.L.). We thank all members of our lab for critical discussions and valuable comments.

Publisher Copyright:
© 2023 The Author(s)

Keywords

  • Biochemistry methods
  • Functional aspects of cell biology
  • Methodology in biological sciences

ASJC Scopus subject areas

  • General

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