Can Zebrafish Unmask the Secrets of Abnormal Skin Pigmentation?

🔍 Key Finding Zebrafish, with their transparent embryos and genetic similarities to humans, are a valuable model for studying abnormal skin pigmentation. Researchers use physical, chemical, and genetic methods to create zebrafish models, offering insights into melanin production pathways and potential treatments for pigmentation disorders.

🔬 Methodology Overview

• Design: Comprehensive narrative review.
• Data Sources: PubMed, Web of Science, and Scopus databases.
• Selection Criteria: English-language experimental studies published between 2000 and 2023 focusing on zebrafish models for skin pigmentation. Articles focusing on other animal models or not directly related to zebrafish skin pigmentation were excluded.
• Analysis Approach: Qualitative synthesis and summary of findings related to zebrafish skin structure, melanin production in zebrafish, and methods for establishing abnormal skin pigmentation models in zebrafish (physical, chemical, and genetic). Discussion of advantages, disadvantages, challenges, and future perspectives of using zebrafish for skin pigmentation research.
• Scope: Zebrafish as a model organism for investigating abnormal skin pigmentation mechanisms.

📊 Results

• Zebrafish share approximately 87% genetic similarity with humans, and melanin production pathways are highly conserved, making them a relevant model for studying human pigmentation disorders.
• UVB exposure at various intensities and durations (e.g., 300 mJ/cm² daily for 5 days, 8100 mJ/cm² over 5 days) darkened zebrafish skin, increased melanin content, and triggered hormone secretion related to pigmentation.
• 5-HT (serotonin) exposure (0.01-1 mM) induced a dose-dependent increase in melanin content and melanocyte count in zebrafish embryos, also promoting melanoblast specification and regeneration.
• Fisetin (200-400 μM for 72 hours) enhanced melanin production and tyrosinase activity in zebrafish, likely through modulation of the GSK-3β pathway.
• Flumequine (0-20 μM for 5-15 days) increased skin hyperpigmentation and melanin production in zebrafish larvae, potentially through activation of p38 MAPK and JNK pathways.
• Knockout of the bmp7b gene in zebrafish resulted in increased retinal and skin melanin, demonstrating its role in inhibiting melanin production.
• Xenografting human uveal melanoma cells into zebrafish embryos allowed for the study of melanoma development and pigmentation changes driven by GNA11/GNAQ mutations.

💡 Clinical Impact Zebrafish, with their genetic and physiological similarities to humans, offer a powerful model for studying skin pigmentation disorders, enabling faster drug discovery and personalized treatment strategies. This could lead to more effective therapies for conditions like melasma, vitiligo, and post-inflammatory hyperpigmentation, improving patient outcomes and quality of life.

🤔 Limitations

• Self-healing, immunity, and impacts on overall development persist with UV irradiation.
• Comprehensive evaluations of long-term and acute toxicities of chemical inducers remain scarce.
• Genetically inducing melanoma as the primary approach differs from the pathogenesis of straightforward skin pigmentation disorders.
• Genetic variations alone cannot encapsulate the entirety of hyperpigmentation disorder pathogenesis.
• Development inhibition seen with some genetic modifications (e.g., bmp7b gene knockout).

✨ What It Means For You Zebrafish, with their genetic similarities to humans and transparent skin, offer a powerful model for studying skin pigmentation disorders, allowing for rapid testing of potential treatments. This research accelerates the development of therapies for conditions like melasma and vitiligo by providing a platform for drug screening and exploring the genetic mechanisms underlying these disorders.

Reference Qu J, Yan M, Fang Y, Zhao J, Xu T, Liu F, Zhang K, He L, Jin L, Sun D. Zebrafish in dermatology: a comprehensive review of their role in investigating abnormal skin pigmentation mechanisms. Frontiers in Physiology. 2023;14:1296046. https://doi.org/10.3389/fphys.2023.1296046