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Andrea M. Henle, Josey Muske, Michael Poplawski, Tanisha Perlmutter; The development of pigmentation in new tissue arises from precursor and not migratory melanocytes in a transgenic GNAQQ209L zebrafish model of uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3177.
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© ARVO (1962-2015); The Authors (2016-present)
Transgenic GNAQQ209L zebrafish express a hyperactive, mutated Gα gene in their pigmented cells, melanocytes. This mutation is found in approximately 85% of patients diagnosed with human uveal melanoma and may cause increased proliferation, survival, or migration of melanocytes. We used zebrafish to study the role of GNAQQ209L during pigment regeneration, to ultimately help us better understand how melanocytes develop in the context of oncogenic GNAQ.
We amputated the caudal fin of wild type and transgenic zebrafish to analyze pigmentation changes and determine the origin of melanocytes during regeneration. We asked whether pre-existing melanocytes from adjacent tissue migrate into new tissue post-amputation, or whether unpigmented melanocyte precursors proliferate in regenerated tissue. This study used phenylthiourea to block formation of new pigment and address these two possible outcomes. Pigmentation in the regenerating caudal fin was captured weekly by microscopy until week 7. Analysis of pigmentation in each image was conducted using FIJI (Fiji Is Just ImageJ) software.
We found no significant difference in the area of total pigmentation pre- and post-amputation in fish, but did find that expression of GNAQQ209L increased the total pigmented area compared to wild type zebrafish. We discovered that pigmentation in regenerating tissue in both GNAQQ209L and wild type zebrafish arises from unpigmented melanocyte precursors rather than migration of pre-existing melanocytes.
This research provides a better understanding of how GNAQQ209L affects melanocyte development and regeneration. This study suggests that GNAQQ209L does not play a role in migration of melanocytes during regeneration. Future research in this area will investigate the specific downstream signaling pathways that cause GNAQQ209L-induced hyperproliferation of melanocytes in this zebrafish model. This research has implications in diseases in which melanocytes are hyperproliferative, such as cutaneous melanoma or uveal melanoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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