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Pollutants and temperature are major environmental factors. Using the bristle patterning of <jats:italic>Drosophila<\/jats:italic> as a model system, we observed that cold temperature and methotrexate, a medical drug that contaminates wastewaters, increase dorsocentral (DC) bristle number<jats:italic>,<\/jats:italic> a trait normally robust. The patterning of bristles is well understood and involves the <jats:italic>achaete-scute (ac-sc)<\/jats:italic> proneural genes. Modular enhancers activate <jats:italic>ac-sc<\/jats:italic> expression in groups of cells, called proneural clusters, from which bristle precursors are selected by lateral inhibition, a process involving Notch signalling and <jats:italic>ac-sc<\/jats:italic> auto-activation. In addition, <jats:italic>ac-sc<\/jats:italic> basal expression is controlled by a cocktail of repressive factors. We observed that the deletion of the DC enhancer prevents the induction of ectopic DC bristles by methotrexate but does not stop low temperature to induce DC bristles. Indeed, we show that methotrexate has a strong synergy with mutants of factors that regulate the DC enhancer and extends the zone of activity of this enhancer. In contrast, temperature interacts with repressors of <jats:italic>ac-sc<\/jats:italic> basal expression. Thus, methotrexate and temperature both affect DC bristle patterning but by distinct mechanisms, methotrexate on the DC enhancer and cold independently of this enhancer.<\/jats:p>","DOI":"10.1038\/s41598-025-20122-6","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T10:20:50Z","timestamp":1760610050000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exposome variations affect Drosophila bristle patterning via the regulation of proneural genes through distinct mechanisms"],"prefix":"10.1038","volume":"15","author":[{"given":"Val\u00e9rie","family":"Ribeiro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Doucet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Gho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agn\u00e8s","family":"Audibert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Michel","family":"Gibert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"20122_CR1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3389\/fevo.2019.00056","volume":"7","author":"CP Klingenberg","year":"2019","unstructured":"Klingenberg, C. 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