An ongoing role for Wnt signaling in differentiating melanocytes invivo.

Laura Vibert,Tatiana Subkankulova,Andrea Rocco,Gerardo Aquino,Ines Gehring,Thomas F Schilling,Robert N Kelsh

doi:10.1111/pcmr.12568

Laura Vibert, Tatiana Subkankulova + Show 5 more

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https://doi.org/10.1111/pcmr.12568

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Abstract

SummaryA role for Wnt signaling in melanocyte specification from neural crest is conserved across vertebrates, but possible ongoing roles in melanocyte differentiation have received little attention. Using a systems biology approach to investigate the gene regulatory network underlying stable melanocyte differentiation in zebrafish highlighted a requirement for a positive‐feedback loop involving the melanocyte master regulator Mitfa. Here, we test the hypothesis that Wnt signaling contributes to that positive feedback. We show firstly that Wnt signaling remains active in differentiating melanocytes and secondly that enhanced Wnt signaling drives elevated transcription of mitfa. We show that chemical activation of the Wnt signaling pathway at early stages of melanocyte development enhances melanocyte specification as expected, but importantly that at later (differentiation) stages, it results in altered melanocyte morphology, although melanisation is not obviously affected. Downregulation of Wnt signaling also results in altered melanocyte morphology and organization. We conclude that Wnt signaling plays a role in regulating ongoing aspects of melanocyte differentiation in zebrafish.

Highlights

Melanocytes are a key derivative of the neural crest, and the mechanisms of melanocyte development are of major interest from developmental and stem cell biology and applied biology perspectives, with clear relevance to understanding human pigmentary disease (Yamaguchi and Hearing 2014; White et al, 2011; Speeckaert et al, 2014; Aoude et al, 2015; Mort et al, 2015)
A role for Wnt signaling in melanocyte specification from neural crest is conserved across vertebrates, 8 but possible ongoing roles in melanocyte differentiation have received little attention
We show firstly that Wnt signaling remains active in differentiating melanocytes and secondly that enhanced Wnt signaling drives elevated transcription of mitfa

Summary

Introduction

Melanocytes are a key derivative of the neural crest, and the mechanisms of melanocyte development are of major interest from developmental and stem cell biology and applied biology perspectives, with clear relevance to understanding human pigmentary disease (Yamaguchi and Hearing 2014; White et al, 2011; Speeckaert et al, 2014; Aoude et al, 2015; Mort et al, 2015). Melanocyte specification from neural crest cells has been relatively well-studied, and has illuminated the underlying mechanisms of neurocristopathies like the Waardenburg syndromes (Dutton et al, 2001; Lee et al., 2000; Southard-Smith et al, 1998; Elworthy et al, 2003). 8 property of the state of the gene regulatory network (GRN) in differentiated melanocytes. The combined actions of early Wnt signaling and Sox drive expression of Mitf/Mitfa, which acts as a central node in the melanocyte GRN, activating numerous genes associated with all aspects of melanocyte differentiation (Cheli et al, 2010).

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