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TEADlight,一种用于实时检测YAP/TAZ-TEAD信号传导的明亮动态报告基因。

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

作者信息

Morin Valérie, Le Toquin Yoann, Tepordei Daria, Marcelle Christophe, Delaune Emilie

机构信息

Université Claude Bernard Lyon1, MeLis Laboratory, CNRS, INSERM, Lyon, France.

Université Claude Bernard Lyon1, MeLis Laboratory, CNRS, INSERM, Lyon, France; Monash University, Australian Regenerative Medicine Institute, Clayton, Victoria, Australia.

出版信息

Dev Biol. 2025 Sep;525:194-205. doi: 10.1016/j.ydbio.2025.06.007. Epub 2025 Jun 6.

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.

摘要

YAP/TAZ-TEAD信号通路对于调节细胞增殖或分化至关重要,它是细胞环境中机械力的主要传导器。然而,现有的监测其活性的工具受到灵敏度和动态范围有限的阻碍,特别是在复杂的生物系统中。在此,我们展示了TEADlight,一种用于YAP/TAZ-TEAD活性的高度灵敏的转录报告基因,它由8个多聚化的TEAD结合位点构建而成,驱动一种不稳定的荧光蛋白,并通过翻译元件增强以提高反应性。鸡胚体内电穿孔显示,在神经发生和肌肉发生过程中,随着YAP/TAZ信号的调节,TEADlight发生了变化。此外,TEADlight揭示了体内体节中的动态反应,以及体外的接触抑制和空间限制。因此,TEADlight能够对发育和细胞模型中的YAP/TAZ-TEAD信号进行实时、高灵敏度分析,为研究该信号通路在生理和病理过程中的活性开辟了新途径。

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