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Related Experiment Video

Updated: Sep 3, 2025

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Optogenetic control of YAP cellular localisation and function.

Pearlyn J Y Toh1, Jason K H Lai1, Anke Hermann2

  • 1Mechanobiology Institute, National University of Singapore, Singapore.

EMBO Reports
|July 25, 2022
PubMed
Summary
This summary is machine-generated.

Researchers developed optogenetic YAP (optoYAP) to control the Hippo pathway effector YAP. This tool precisely regulates YAP

Keywords:
YAPcell proliferationoptogeneticsspatiotemporal dynamicszebrafish

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biotechnology

Background:

  • The Hippo signaling pathway effector, YAP, is crucial for organ growth and regeneration.
  • Dysregulated YAP activity drives uncontrolled cell proliferation, contributing to cancer.
  • Targeting YAP offers potential therapeutic strategies for diseases and regeneration.

Purpose of the Study:

  • To develop a versatile optogenetic tool for exogenous regulation of YAP activity.
  • To investigate the spatiotemporal control of YAP localization and function.
  • To explore therapeutic applications of controlled YAP modulation.

Main Methods:

  • Engineered an optogenetic construct (optoYAP) by fusing a light-sensitive LOV2 domain to YAP.
  • The LOV2 domain photocages a nuclear localization signal (NLS), controlling nuclear import of optoYAP with 488 nm light.
  • Validated optoYAP function in cell culture and in vivo (zebrafish embryos).

Main Results:

  • Light-induced unfolding of the LOV2 domain enables tunable, reversible nuclear translocation of optoYAP.
  • Activated optoYAP enhances YAP target gene expression and promotes cell proliferation in vitro.
  • optoYAP modulates gene expression in zebrafish embryos and induces anchorage-independent growth, overriding substrate stiffness cues.

Conclusions:

  • optoYAP provides a powerful, light-inducible system for precise spatiotemporal control of YAP activity.
  • This tool is functional in both cell culture and in vivo models.
  • optoYAP serves as a valuable research tool for fundamental biology and has potential in regenerative medicine and cancer therapy.