Dynamics of Wnt/β-catenin reporter activity throughout whole life in a naturally short-lived vertebrate

Abstract

Wnt/β-catenin signaling plays a major role in regulation of embryogenesis, organogenesis, and adult tissue homeostasis and regeneration. However, the roles played by Wnt/β-catenin and the spatiotemporal regulation of its activity throughout life, including during aging, are not fully understood. To address these issues, we introduced a Wnt/β-catenin signaling sensitive reporter into African turquoise killifish (Nothobranchius furzeri), a naturally ultra-short-lived fish that allows for the analysis of its whole life within a short period of time. Using this reporter killifish, we unraveled the previously unidentified dynamics of Wnt/β-catenin signaling during development and aging. Using the reporter strain, we detected Wnt/β-catenin activity in actively developing tissues as reported in previous reports, but also observed activation and attenuation of Wnt/β-catenin activity during embryonic reaggregation and diapause, respectively. During the aging process, the reporter was activated in the choroidal layer and liver, but its expression decreased in the kidneys. In addition, the reporter also revealed that aging disrupts the spatial regulation and intensity control of Wnt/β-catenin activity seen during fin regeneration, which interferes with precise regeneration. Thus, the employed reporter killifish is a highly useful model for investigating the dynamics of Wnt/β-catenin signaling during both the developmental and aging process.