Direct Photoreception and Decentralized Clocks in the Zebrafish Circadian System

Abstract: Circadian rhythms are fundamental, endogenously generated biological mechanisms that have evolved to synchronize organisms with the diurnal cycles resulting from Earth's rotation. The zebrafish (Danio rerio) has emerged as a uniquely powerful and increasingly pivotal model for investigating these rhythms due to its unique combination of features: optical transparency during embryonic and larval stages, rapid external development, genetic tractability, and high evolutionary conservation of core circadian clock genes and neural pathways with humans. A particularly distinctive trait is the intrinsic photosensitivity and autonomous circadian oscillatory capacity found in cells throughout the zebrafish body, including peripheral organs and tissues. This provides a distinctive system for dissecting the coordinated and independent regulation of central and peripheral clocks. This review systematically synthesizes recent advances in zebrafish circadian research, focusing on the molecular architecture of the core clock, the redundant multi-tissue light-input pathways, and the clock's precise regulation of key physiological processes such as neural function, cardiovascular activity, metabolism, immunity, and reproduction. We further discuss current limitations and challenges, including the mapping of relevant neural circuits, understanding inter-tissue communication, and conducting lifespan-wide investigations. Finally, we outline promising future directions, such as leveraging emerging technologies for circuit analysis, exploring the impact of environmental disruptors, and advancing translational medical applications.