TEADlight, a bright dynamic reporter for live detection of YAP/TAZ-TEAD signaling

Abstract

The YAP/TAZ-TEAD pathway is crucial for regulating cell proliferation or differentiation, serving as a major transducer of mechanical forces from the cellular environment. However, existing tools to monitor its activity are hindered by limited sensitivity and dynamic range, particularly in complex biological systems. Here, we present TEADlight, a highly sensitive transcriptional reporter for YAP/TAZ-TEAD activity, constructed with 8 multimerized TEAD-binding sites driving a destabilized fluorescent protein, enhanced with translational elements for improved responsiveness. In vivo electroporation in the chicken embryo showed TEADlight changes, consequently to modulations in YAP/TAZ signaling during neurogenesis and myogenesis. Moreover, TEADlight revealed dynamic responses in somites in vivo, and to contact inhibition and spatial constraints in vitro. Therefore, TEADlight enables real-time, high-sensitivity analysis of YAP/TAZ-TEAD signaling across developmental and cellular models, opening new avenues for studying the activity of this pathway in physiological and pathological processes.

Keywords: TAZ; TEAD; TEADlight; Transcriptional reporter; YAP.