biostudies-literatureUnknownYevdash JINIDCR NIH HHSNCI NIH HHSNIGMS NIH HHSMelanocytes reside in diverse microenvironments that influence their susceptibility to oncogenic transformation, however, studying rare melanoma subsets has been hindered by the lack of suitable animal models. We developed a primary, immune-competent zebrafish model to study uveal melanoma (UM), utilizing choroidal-targeted injection and electroporation of plasmids containing human <i>GNAQ</i> ^Q209L and CRISPR/Cas9 cassettes for tumor suppressor gene deletion. Single-cell transcriptional profiling of genetically identical eye- and skin-derived tumors revealed distinct oncogenic pathways, highlighting the importance of studying melanoma subtypes in their correct anatomical context. Additionally, we identified a population of <i>tfec</i> - and <i>pax3a</i> -expressing melanocyte pbioRxiv : the preprint server for biology2025.05.05.652300https://www.ebi.ac.uk/biostudies/studies/S-EPMC12431003biostudies-literatureMitfa-Independent Melanocyte Progenitors are Highly Susceptible to GNAQ-induced Uveal Melanoma in Adult Zebrafish.PMC12431003T90 DE023520P30 CA086862T32 GM144636Binkley EMCornell RALang DMoore RMontgomery CFriend DKenny CO'Toole IYevdash JIWeigel RJGutelius DLi ZRiordan JDupuy AMoore SPGRobinson DCampbell-Hanson KRfalseMitfa-Independent Melanocyte Progenitors are Highly Susceptible to GNAQ-induced Uveal Melanoma in Adult Zebrafish.Melanocytes reside in diverse microenvironments that influence their susceptibility to oncogenic transformation, however, studying rare melanoma subsets has been hindered by the lack of suitable animal models. We developed a primary, immune-competent zebrafish model to study uveal melanoma (UM), utilizing choroidal-targeted injection and electroporation of plasmids containing human <i>GNAQ</i> ^Q209L and CRISPR/Cas9 cassettes for tumor suppressor gene deletion. Single-cell transcriptional profiling of genetically identical eye- and skin-derived tumors revealed distinct oncogenic pathways, highlighting the importance of studying melanoma subtypes in their correct anatomical context. Additionally, we identified a population of <i>tfec</i> - and <i>pax3a</i> -expressing melanocyte p2025-01-01T00:00:00Z2025 Sep2026-04-27T03:12:53.865Z2026-04-27T03:09:25.639ZS-EPMC124310034095014610.1101/2025.05.05.652300