El Mir J et al. (2024), Xenopus as a model system for studying pigmenta...

XB-ART-60748

Pigment Cell Melanoma Res 2024 Jan 07;381:e13178. doi: 10.1111/pcmr.13178.

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Xenopus as a model system for studying pigmentation and pigmentary disorders.

El Mir J , Nasrallah A , Thézé N , Cario M , Fayyad-Kazan H , Thiébaud P , Rezvani HR .

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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.

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Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: angptl4 atp6v0c bmpr1b braf dct dse edn3 ednrb ets1 foxd3 mitf msx1 nlgn1 otogl2 pax3 rab27a raf1 shh shroom2 slc24a5 slc45a2 snai2 sox10 sox2 tyr tyrp1
GO keywords: angiogenesis [+]

???displayArticle.disOnts??? oculocutaneous albinism [+]
Phenotypes: Xla Wt + benzoic acid (Fig. 5 b) [+]

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	FIGURE 1 Adult Xenopus and human skin. (a) Schematic representation of the skin of Xenopus. (b, c) Morphology of adult Xenopus (b) and human (c) skin with white lines demarcating epidermis (Ep), dermis (De) and hypodermis (Hd). A smaller mucous (Mu) and larger granular (Gr) gland and melanocytes (Mel) are indicated in (b). Stratum germinativum (SG), Stratum spinosum (SSp) and Stratum corneum (Sco) are indicated. Human sebaceous glands (SG), sweat glands (SW) and hair follicle (HF) are indicated in C. Reproduced with permission from Meier 2013. PLoS One 8, e73596. Public Library of Science.
	FIGURE 2 Architecture of the epidermis of Xenopus embryo. (a) Schematic representation of dorsal embryo skin. (b) Schematic representation of the epidermis in a transverse section with ciliated cells, ionocytes, goblet cells and small secretory cells (SSCs). Otogelin-like is a major secretory glycoprotein produced by goblet cells and SSCs. Goblet cells also secrete the epidermal lectin (Xeel). SCs cells also secrete substrates that have not yet been identified. Additionally, secretions contain innate defense molecules such as vitellogenin, apolipoprotein β, complement factors (C3 and C9) and FCGBP/FCGBP-like proteins. The image was created with the aid of BioRender. (c) Ultrastructure of the epidermis. View of the mucociliary epithelium including a ciliated cell and several goblet cells. Reproduced with permission from Hayes 2007. Developmental Biology, 312, 115–130, Elsevier.
	FIGURE 3 Pigment cell in Xenopus embryo at different developmental stages. (a) Development of X. laevis embryos from the fertilized egg to 3-day-old tadpole. (b) Lateral view of a stage 33/34 embryo. (c) Lateral view of a stage 42 embryo. (d) Dorsal view of stage 48 embryo head. (e) Lateral region of stage 48 tadpole showing the dendritic aspect of melanocytes. Scale bar 1 mm in b, c and d and 250 μm in e. Personal communication.
	FIGURE 4 Xenopus melanogenesis. Upper part, the vertebrate melanocyte lineage. Melanoblasts originating from SOX10 neural crest progenitor express MITF and differentiate into melanocytes that express melanin biosynthesis enzymes DCT, TYR and TYRP1. Lower part, gene expression of mitf (a), tyrosinase (b) and dct (c) in Xenopus embryo revealed by in situ hybridization. Expression of the corresponding genes is indicated by an arrowhead. Personal communication.


	tyr (tyrosinase) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 28-29, lateral view, anterior left, dorsal up.
	FIGURE 1. Adult Xenopus and human skin. (a) Schematic representation of the skin of Xenopus. (b, c) Morphology of adult Xenopus (b) and human (c) skin with white lines demarcating epidermis (Ep), dermis (De) and hypodermis (Hd). A smaller mucous (Mu) and larger granular (Gr) gland and melanocytes (Mel) are indicated in (b). Stratum germinativum (SG), Stratum spinosum (SSp) and Stratum corneum (Sco) are indicated. Human sebaceous glands (SG), sweat glands (SW) and hair follicle (HF) are indicated in C. Reproduced with permission from Meier 2013. PLoS One 8, e73596. Public Library of Science.
	FIGURE 2. Architecture of the epidermis of Xenopus embryo. (a) Schematic representation of dorsal embryo skin. (b) Schematic representation of the epidermis in a transverse section with ciliated cells, ionocytes, goblet cells and small secretory cells (SSCs). Otogelin‐like is a major secretory glycoprotein produced by goblet cells and SSCs. Goblet cells also secrete the epidermal lectin (Xeel). SCs cells also secrete substrates that have not yet been identified. Additionally, secretions contain innate defense molecules such as vitellogenin, apolipoprotein β, complement factors (C3 and C9) and FCGBP/FCGBP‐like proteins. The image was created with the aid of BioRender. (c) Ultrastructure of the epidermis. View of the mucociliary epithelium including a ciliated cell and several goblet cells. Reproduced with permission from Hayes 2007. Developmental Biology, 312, 115–130, Elsevier.
	FIGURE 3. Pigment cell in Xenopus embryo at different developmental stages. (a) Development of X. laevis embryos from the fertilized egg to 3‐day‐old tadpole. (b) Lateral view of a stage 33/34 embryo. (c) Lateral view of a stage 42 embryo. (d) Dorsal view of stage 48 embryo head. (e) Lateral region of stage 48 tadpole showing the dendritic aspect of melanocytes. Scale bar 1 mm in b, c and d and 250 μm in e. Personal communication.
	FIGURE 4. Xenopus melanogenesis. Upper part, the vertebrate melanocyte lineage. Melanoblasts originating from SOX10 neural crest progenitor express MITF and differentiate into melanocytes that express melanin biosynthesis enzymes DCT, TYR and TYRP1. Lower part, gene expression of mitf (a), tyrosinase (b) and dct (c) in Xenopus embryo revealed by in situ hybridization. Expression of the corresponding genes is indicated by an arrowhead. Personal communication.
	FIGURE 5. Examples of pigment modification in stage 42 Xenopus embryo after different treatments. (a) Untreated control embryo. (b) Total pigment loss phenotype upon treatment with NSC86153 compound. (c) Segmented pattern on the dorsal side upon treatment with NSC84093 compound. (d–f) Effect of sex steroids on the epidermal pigmented area of tadpoles in the presence of increased estradiol treatment (+E2 and ++E2). (g, h) Maltol treatment (H, +Maltol) of embryo stimulates melanocyte aggregation compared to untreated control embryo (G). (i, j) Inhibition of melanocyte migration in endothelin‐3 signaling depleted embryo (j, −ET3) compared to control embryo. (k, l) Embryos grown in the light versus dark exhibit distinct pigmentation of their head. (b, c) Reproduced with permission from Tomlinson 2009 Mol.BiolSyst 5376–384, The Royal Society of Chemistry Publishing. (d–f) Reproduced with permission from Castillo‐Briceno 2014, Fontiers in zoology 11:9, Springer Nature. (g, h) Reproduced with permission from Dahora, Environ Toxicol Chem 39(2), 381–395, John Wyley & Sons. (i, j) Reproduced with permission from Yamamoto 2011 Dev Dyn 240, 1454–1466, John Wyley & Sons. (k, l) Reproduced with permission from Bertolesi 2016 Pigment Cell Melanoma Res 29, 688–70, John Wiley & Sons.
	FIGURE 6. Xenopus embryo as a model for ultraviolet radiation (UVR) response. (a–c) Phenotypic aspect of melanocytes 5 and 10 min after UVR compared to non‐irradiated (NIR) control embryo. Red arrowhead marks a melanocyte with dendritic extension induced by UVR. (d) Histological transverse section of an embryo stained by hematoxylin–eosin showing epiderm thickening after UVR, IR irradiated side, NIR non irradiated control side. Red arrowheads marks the regions enlarged views shown in E and F. (e,f) Enlargement of the irradiated side epiderm (IR, left) versus nonirradiated side (NIR, right) stained by hematoxylin–eosin (e) or immunostained with anti‐keratin 2 (KER) antibody (f). (g) Immunostaining analysis of a histological section at the level of the head of a stage 42 irradiated embryo. CPDs (red arrow) are found on the irradiated side (IR) but absent from the nonirradiated side (NIR). Br, brain. Reproduced with permission from El Mir 2023, Dev Growth Differ. 65, 194–202. John Wiley & Sons.