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      Wnt5a Inhibits the Proliferation and Melanogenesis of Melanocytes

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          Abstract

          Wnt5a, which is a noncanonical Wnt molecule, has been shown to be involved in a variety of developmental processes and cellular functions. In this study, we used “melan-a” cells as a cell model to investigate the effects of Wnt5a on melanocyte proliferation and melanogenesis, and to elucidate the possible mechanisms involved. We infected melan-a cells with recombinant Wnt5a adenoviruses to express Wnt5a protein and to simulate the Wnt5a processing environment. MTT assay and BrdU incorporation assay revealed that Wnt5a significantly inhibited the proliferation of melan-a cells. Melanin content and tyrosinase activity assays showed that Wnt5a was an inhibitor of melanin synthesis. Furthermore, RT-PCR and Western blot showed that this suppressive effect depended on noncanonical Wnt/Ror2 pathway activation and accessed the inhibition of the canonical Wnt pathway. The above results provided a novel insight into the role of Wnt5a and its related signaling in melanocyte homeostasis.

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          Most cited references30

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          Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma.

          Gene expression profiling identified human melanoma cells demonstrating increased cell motility and invasiveness. The gene WNT5A best determined in vitro invasive behavior. Melanoma cells were transfected with vectors constitutively overexpressing Wnt5a. Consistent changes included actin reorganization and increased cell adhesion. No increase in beta-catenin expression or nuclear translocation was observed. There was, however, a dramatic increase in activated PKC. In direct correlation with Wnt5a expression and PKC activation, there was an increase in melanoma cell invasion. Blocking this pathway using antibodies to Frizzled-5, the receptor for Wnt5a, inhibited PKC activity and cellular invasion. Furthermore, Wnt5a expression in human melanoma biopsies directly correlated to increasing tumor grade. These observations support a role for Wnt5a in human melanoma progression.
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            The regulation of skin pigmentation.

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              Control of neural crest cell fate by the Wnt signalling pathway.

              Environmental signals are important in the development of neural crest, during which process multipotent progenitor must choose from several fates. However, the nature of these environmental signals is unknown. A previous fate map of zebrafish cranial neural crest showed that lineage-restricted clones of pigment cells arise from medial cells near the neural keel, and that clones of neurons arise from lateral cells farther from the neural keel. Wnt-1 and Wnt-3a are candidate genes for influencing neural crest fate, as they are expressed next to medial, but not lateral, crest cells. Here we determine the role of Wnt signals in modulating the fate of neural crest by injecting messenger RNAs into single, premigratory neural crest cells of zebrafish. Lineage analysis of injected cells shows that activation of Wnt signalling by injection of mRNA encoding cytoplasmic beta-catenin promotes pigment-cell formation at the expense of neurons and glia. Conversely, inhibition of the Wnt pathway, by injection of mRNAs encoding either a truncated form of the transcription factor Tcf-3 or a dominant-negative Wnt, promotes neuronal fates at the expense of pigment cells. We conclude that endogenous Wnt signalling normally promotes pigment-cell formation by medial crest cells and thereby contributes to the diversity of neural crest cell fates.
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                Author and article information

                Journal
                Int J Med Sci
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2013
                5 April 2013
                : 10
                : 6
                : 699-706
                Affiliations
                1. Department of Cell Biology, Third Military Medical University, Chongqing 400038, China;
                2. The Third Military Medical University group 5, Third Military Medical University, Chongqing 400038, China;
                3. Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing 400016, China.
                Author notes
                ✉ Corresponding author: Tel.: 86-023-68753260; Email: ghy0601@ 123456126.com .

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijmsv10p0699
                10.7150/ijms.5664
                3619119
                23569434
                9b7a0db7-631b-482a-a408-c53c9b39cc16
                © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                History
                : 6 December 2012
                : 17 March 2013
                Categories
                Research Paper

                Medicine
                melanocyte,melanogenesis,proliferation,wnt5a,wnt/ror2 pathway.
                Medicine
                melanocyte, melanogenesis, proliferation, wnt5a, wnt/ror2 pathway.

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