Translational zebrafish model for molecular and developmental pathways of melanogenesis and pigmentation dysfunctions in humans

The skin colour is determined by melanin which is the brownish black pigment of Melanocytes. It is produced through melanogenesis. The melanin is crucial for protection of DNA from UV damage and it absorbs excess radiation. Skin pigmentation-related disorders such as albinism, melasma, and melanoma frequently arise due to dysregulation of the melanogenesis process. The traditional animal models, mice, rat, rabbits and Guinea pigs often fall short due to their time-consuming generation process, intricate operations, and high costs. As a result, researchers have turned to explore alternative models, zebrafish (Danio rerio). The zebrafish, with its unique skin structure and melanin production mechanism, offers several advantages as a model animal. The similarities between skin structure of zebrafish and mammals, its visible melanin development in melanophores and the conserved melanogenesis pathways and high reproductive capacity makes it suitable model organism to explore the bases of diverse skin ailments and possible treatment targets and strategies. This review highlights the challenges, potential improvements, and future directions in using zebrafish for pigmentation disorder research. This review uniquely emphasizes zebrafish as a rapid, cost-effective, genetically conserved model and high-throughput model to bridge molecular mechanisms of melanogenesis with human pigmentation disorders. Melanin plays a central role in skin pigmentation and DNA protection, and its dysregulation leads to disorders like albinism, melasma, and melanoma. Conventional mammalian models are limited by high cost, long generation time, and complex handling. Zebrafish offer a rapid, cost-effective, and genetically conserved model to study melanogenesis and pigmentation disorders. The transparent skin and visible melanophore development in zebrafish allow real-time analysis of pigment formation and related cellular defects.