WNT1 and WNT3a promote expansion of melanocytes through distinct modes of action

Authors

  • Karen Joyce Dunn,

    1. Mouse Embryology Section, Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA
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  • Matthew Brady,

    1. Mouse Embryology Section, Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA
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  • Christina Ochsenbauer-Jambor,

    1. Department of Microbiology, University of Alabama, Birmingham, AL, USA
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  • Sara Snyder,

    1. Mouse Embryology Section, Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA
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  • Arturo Incao,

    1. Mouse Embryology Section, Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA
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  • William J. Pavan

    Corresponding author
    1. Mouse Embryology Section, Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA
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Address correspondence to William J. Pavan, e-mail: bpavan@nhgri.nih.gov

Summary

WNT1 and WNT3a have been described as having redundant roles in promoting the development of neural crest-derived melanocytes (NC-Ms). We used cell lineage restricted retroviral infections to examine the effects of WNT signaling on defined cell types in neural crest cultures. RCAS retroviral infections were targeted to melanoblasts (NC-M precursor cells) derived from transgenic mice that express the virus receptor, TVA, under the control of a melanoblast promoter (DCT). As expected, over 90% of DCT–TVA+ cells expressed early melanoblast markers MITF and KIT. However, by following the fate of infected cells in standard culture conditions, we find that only 5% of descendents were NC-Ms. The majority of the descendents were not NC-Ms, but expressed smooth muscle cell markers, demonstrating that mammalian melanoblasts are not committed to the NC-M lineage. RCAS infection of DCT–TVA+ cells demonstrated that overexpression of canonical WNT signaling genes (βCAT, WNT3a or WNT1) can increase NC-M numbers in an endothelin dependent manner. However, WNT1 and WNT3a have different modes of action with respect to melanoblast fate. Intrinsic over-expression of βCAT or WNT3a can increase NC-M numbers by biasing the fate of DCT–TVA+ cells to NC-Ms. In contrast, the DCT–TVA+ melanoblasts cannot respond to WNT1 signaling and do not alter their fate towards NC-M. Instead, WNT1 only increases NC-M numbers through paracrine signaling on melanoblast precursors to increase the numbers of neural crest cells that become NC-Ms.

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