Program in Molecular Medicine; Department of Molecular Cell, and Cancer Biology; Graduate School of Biomedical Sciences
Cancer Biology | Cells | Cellular and Molecular Physiology | Developmental Biology | Embryonic Structures
Preventing terminal differentiation is important in the development and progression of many cancers including melanoma. Recent identification of the BMP ligand GDF6 as a novel melanoma oncogene showed GDF6-activated BMP signaling suppresses differentiation of melanoma cells. Previous studies have identified roles for GDF6 orthologs during early embryonic and neural crest development, but have not identified direct regulation of melanocyte development by GDF6. Here, we investigate the BMP ligand gdf6a, a zebrafish ortholog of human GDF6, during the development of melanocytes from the neural crest. We establish that the loss of gdf6a or inhibition of BMP signaling during neural crest development disrupts normal pigment cell development, leading to an increase in the number of melanocytes and a corresponding decrease in iridophores, another neural crest-derived pigment cell type in zebrafish. This shift occurs as pigment cells arise from the neural crest and depends on mitfa, an ortholog of MITF, a key regulator of melanocyte development that is also targeted by oncogenic BMP signaling. Together, these results indicate that the oncogenic role ligand-dependent BMP signaling plays in suppressing differentiation in melanoma is a reiteration of its physiological roles during melanocyte development.
cancer biology, developmental biology, zebrafish, UMCCTS funding
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© 2019, Gramann et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Elife. 2019 Dec 23;8. pii: e50047. doi: 10.7554/eLife.50047. [Epub ahead of print] Link to article on publisher's site
Gramann A, Venkatesan AM, Guerin M, Ceol CJ. (2019). Regulation of zebrafish melanocyte development by ligand-dependent BMP signaling. Open Access Articles. https://doi.org/10.7554/eLife.50047. Retrieved from https://escholarship.umassmed.edu/oapubs/4090
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This work is licensed under a Creative Commons Attribution 4.0 License.