Xenopus as a model system for studying pigmentation and pigmentary disorders

Abstract

Human pigmentary disorders encompass a broad spectrum of phenotypic changes arising from disruptions in various stages of melanocyte formation, the melanogenesis process, or the transfer of pigment from melanocytes to keratinocytes. A large number of pigmentation genes associated with pigmentary disorders have been identified, many of them awaiting in vivo confirmation. A more comprehensive understanding of the molecular basis of pigmentary disorders requires a vertebrate animal model where changes in pigmentation are easily observable in vivo and can be combined to genomic modifications and gain/loss‐of‐function tools. Here we present the amphibian Xenopus with its unique features that fulfill these requirements. Changes in pigmentation are particularly easy to score in Xenopus embryos, allowing whole‐organism based phenotypic screening. The development and behavior of Xenopus melanocytes closely mimic those observed in mammals. Interestingly, both Xenopus and mammalian skins exhibit comparable reactions to ultraviolet radiation. This review highlights how Xenopus constitutes an alternative and complementary model to the more commonly used mouse and zebrafish, contributing to the advancement of knowledge in melanocyte cell biology and related diseases.

Methodological and Ethical Considerations in the Use of Chordate Embryos in Biomedical Research

“…Recently, this model has been proposed for studying pigmentation and pigment disorders, as pigmentation changes in Xenopus embryos are easily observable, and their melanocytes respond similarly to those of mammals when exposed to ultraviolet radiation [ 58 ]. For toxicity testing, amphibian embryos are recommended for preliminary tests that will need to be complemented by other tests, such as those in rodents [ 59 ].…”

Methodological and Ethical Considerations in the Use of Chordate Embryos in Biomedical Research

“…Recently, this model has been proposed for studying pigmentation and pigment disorders, as pigmentation changes in Xenopus embryos are easily observable, and their melanocytes respond similarly to those of mammals when exposed to ultraviolet radiation [ 58 ]. For toxicity testing, amphibian embryos are recommended for preliminary tests that will need to be complemented by other tests, such as those in rodents [ 59 ].…”

Disruption of mc1r Disturbs Skin Pigmentation in Xenopus tropicalis

“…Despite its utility, the genetic mechanisms underlying skin pigmentation in Xenopus tropicalis have not been thoroughly investigated (El Mir et al. 2025 ; Liang et al. 2024 ; Yi et al.…”

“…Xenopus tropicalis has emerged as a valuable model organism for developmental and genetic studies due to its diploid genome, short generation time, and well-established genome editing tools (Carotenuto et al 2023;El Mir et al 2025;Ran, Li, Cheng, et al 2024;Ran et al 2022;Ran, Li, Xu, et al 2024;Willsey et al 2024;Yi et al 2025). Despite its utility, the genetic mechanisms underlying skin pigmentation in Xenopus tropicalis have not been thoroughly investigated (El Mir et al 2025;Liang et al 2024;Yi et al 2025). Understanding the function of pigmentation-related genes like mc1r in this species could provide valuable insights into the evolutionary conservation and diversification of pigmentation pathways across vertebrates.…”

Evolutionary adaptations of TRPA1 thermosensitivity and skin thermoregulation in vertebrates

“…To explore a possible link, we first analyzed the thermosensor role for Trpa1 in the skin pigmentation of ectotherms, turning to Xenopus laevis as we and others have shown it is an excellent model to identify the molecular mechanisms that underlie the regulation of skin pigmentation. 14 , 34 Second, we conducted an evolutionary study, comparing the thermal sensitivity of TRPA1 in related extant species of chordates based on electrophysiological data from the literature. Our analysis focused on the role of the integument for thermoregulation.…”

Methodological and Ethical Considerations in the Use of Chordate Embryos in Biomedical Research

“…Recently, this model has been proposed for studying pigmentation and pigment disorders, as pigmentation changes in Xenopus embryos are easily observable, and their melanocytes respond similarly to those of mammals when exposed to ultraviolet radiation [ 58 ]. For toxicity testing, amphibian embryos are recommended for preliminary tests that will need to be complemented by other tests, such as those in rodents [ 59 ].…”

Disruption of mc1r Disturbs Skin Pigmentation in Xenopus tropicalis

“…Despite its utility, the genetic mechanisms underlying skin pigmentation in Xenopus tropicalis have not been thoroughly investigated (El Mir et al. 2025 ; Liang et al. 2024 ; Yi et al.…”

“…Xenopus tropicalis has emerged as a valuable model organism for developmental and genetic studies due to its diploid genome, short generation time, and well-established genome editing tools (Carotenuto et al 2023;El Mir et al 2025;Ran, Li, Cheng, et al 2024;Ran et al 2022;Ran, Li, Xu, et al 2024;Willsey et al 2024;Yi et al 2025). Despite its utility, the genetic mechanisms underlying skin pigmentation in Xenopus tropicalis have not been thoroughly investigated (El Mir et al 2025;Liang et al 2024;Yi et al 2025). Understanding the function of pigmentation-related genes like mc1r in this species could provide valuable insights into the evolutionary conservation and diversification of pigmentation pathways across vertebrates.…”

Evolutionary adaptations of TRPA1 thermosensitivity and skin thermoregulation in vertebrates

“…To explore a possible link, we first analyzed the thermosensor role for Trpa1 in the skin pigmentation of ectotherms, turning to Xenopus laevis as we and others have shown it is an excellent model to identify the molecular mechanisms that underlie the regulation of skin pigmentation. 14 , 34 Second, we conducted an evolutionary study, comparing the thermal sensitivity of TRPA1 in related extant species of chordates based on electrophysiological data from the literature. Our analysis focused on the role of the integument for thermoregulation.…”

Methodological and Ethical Considerations in the Use of Chordate Embryos in Biomedical Research

“…Recently, this model has been proposed for studying pigmentation and pigment disorders, as pigmentation changes in Xenopus embryos are easily observable, and their melanocytes respond similarly to those of mammals when exposed to ultraviolet radiation [ 58 ]. For toxicity testing, amphibian embryos are recommended for preliminary tests that will need to be complemented by other tests, such as those in rodents [ 59 ].…”

Disruption of mc1r Disturbs Skin Pigmentation in Xenopus tropicalis

“…Despite its utility, the genetic mechanisms underlying skin pigmentation in Xenopus tropicalis have not been thoroughly investigated (El Mir et al. 2025 ; Liang et al. 2024 ; Yi et al.…”

“…Xenopus tropicalis has emerged as a valuable model organism for developmental and genetic studies due to its diploid genome, short generation time, and well-established genome editing tools (Carotenuto et al 2023;El Mir et al 2025;Ran, Li, Cheng, et al 2024;Ran et al 2022;Ran, Li, Xu, et al 2024;Willsey et al 2024;Yi et al 2025). Despite its utility, the genetic mechanisms underlying skin pigmentation in Xenopus tropicalis have not been thoroughly investigated (El Mir et al 2025;Liang et al 2024;Yi et al 2025). Understanding the function of pigmentation-related genes like mc1r in this species could provide valuable insights into the evolutionary conservation and diversification of pigmentation pathways across vertebrates.…”

Evolutionary adaptations of TRPA1 thermosensitivity and skin thermoregulation in vertebrates

“…To explore a possible link, we first analyzed the thermosensor role for Trpa1 in the skin pigmentation of ectotherms, turning to Xenopus laevis as we and others have shown it is an excellent model to identify the molecular mechanisms that underlie the regulation of skin pigmentation. 14 , 34 Second, we conducted an evolutionary study, comparing the thermal sensitivity of TRPA1 in related extant species of chordates based on electrophysiological data from the literature. Our analysis focused on the role of the integument for thermoregulation.…”