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By using automated-microscopy and machine-learning-assisted morphology analysis of primary human melanocytes in co-culture, we performed combinatorial interrogation of melanocyte genotypic variants and functional assessment of lentivirus-introduced mutations. Keratinocyte-induced melanocyte dendricity, an indicator of melanocyte differentiation, was reduced in the melanocortin 1 receptor (MC1R) R\/R variant strain and by NRAS.Q61K and BRAF.V600E expression, while expression of CDK4.R24C and RAC1.P29S had no detectable effect. Time-lapse tracking of melanocytes in co-culture revealed dynamic interaction phenotypes and hyper-motile cell states that indicated that, in addition to the known role in activating mitogenic signalling, MEK-pathway-activating mutations may also allow melanocytes to escape keratinocyte control and increase their invasive potential. Expanding this combinatorial platform will identify other therapeutic target mutations and melanocyte genetic variants, as well as increase understanding of skin cell interactions.<\/jats:p>","DOI":"10.1242\/jcs.234716","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T14:24:11Z","timestamp":1574691851000},"source":"Crossref","is-referenced-by-count":5,"title":["Melanoma mutations modify melanocyte dynamics in co-culture with keratinocytes or fibroblasts"],"prefix":"10.1242","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5301-302X","authenticated-orcid":false,"given":"Dubravka","family":"\u0160kalamera","sequence":"first","affiliation":[{"name":"Mater Research Institute, University of Queensland, Translational Research Institute 1 , Brisbane, 4102 QLD , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander J.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Mater Research Institute, University of Queensland, Translational Research Institute 1 , Brisbane, 4102 QLD , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Ehmann","sequence":"additional","affiliation":[{"name":"Mater Research Institute, University of Queensland, Translational Research Institute 1 , Brisbane, 4102 QLD , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen A.","family":"Ainger","sequence":"additional","affiliation":[{"name":"Dermatology Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute 2 , Brisbane, 4102 QLD , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Lanagan","sequence":"additional","affiliation":[{"name":"Mater Research Institute, University of Queensland, Translational Research Institute 1 , Brisbane, 4102 QLD , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Sturm","sequence":"additional","affiliation":[{"name":"Dermatology Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute 2 , Brisbane, 4102 QLD , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Gabrielli","sequence":"additional","affiliation":[{"name":"Mater Research Institute, University of Queensland, Translational Research Institute 1 , Brisbane, 4102 QLD , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2019,12,13]]},"reference":[{"key":"2024061318413811400_JCS234716C1","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1111\/j.1600-0625.2011.01293.x","article-title":"Effect of MC1R variant allele status on MSH-ligand induction of dopachrome tautomerase in melanocytes co-cultured with keratinocytes","volume":"20","author":"Ainger","year":"2011","journal-title":"Exp. 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