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

A 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 organisation. We conclude that Wnt signaling plays a role in regulating ongoing aspects of melanocyte differentiation in zebrafish. This article is protected by copyright. All rights reserved.