UMMS Affiliation

Program in Molecular Medicine; Department of Molecular Cell, and Cancer Biology; Graduate School of Biomedical Sciences

Publication Date

2019-12-23

Document Type

Article

Disciplines

Cancer Biology | Cells | Cellular and Molecular Physiology | Developmental Biology | Embryonic Structures

Abstract

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.

Keywords

cancer biology, developmental biology, zebrafish, UMCCTS funding

Rights and Permissions

© 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

10.7554/eLife.50047

Source

Elife. 2019 Dec 23;8. pii: e50047. doi: 10.7554/eLife.50047. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

eLife

Related Resources

Link to Article in PubMed

PubMed ID

31868592

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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