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We evaluated the effects of retinoic acid on palate fusion and WNT signaling in in vitro explant cultures. Unfused palates from E13.5 mouse embryos were cultured for 4 days with 0.5\u00a0\u03bcM, 2\u00a0\u03bcM or without retinoic acid. Apoptosis, proliferation, WNT signaling and bone formation were analyzed by histology and quantitative PCR. Retinoic acid treatment with 0.5 and 2.0\u00a0\u03bcM reduced palate fusion from 84% (SD 6.8%) in the controls to 56% (SD 26%) and 16% (SD 19%), respectively. Additionally, 2\u00a0\u03bcM retinoic acid treatment increased <jats:italic>Axin2<\/jats:italic> expression. Retinoic acid also increased the proliferation marker <jats:italic>Pcna<\/jats:italic> as well as the number of Ki\u201067\u2010positive cells in the palate epithelium. At the same time, the WNT inhibitors <jats:italic>Dkk1, Dkk3, Wif1<\/jats:italic> and <jats:italic>Sfrp1<\/jats:italic> were downregulated at least two\u2010fold. Retinoic acid also down\u2010regulated <jats:italic>Alpl<\/jats:italic> and <jats:italic>Col1a2<\/jats:italic> gene expression. Alkaline phosphatase (ALP) activity was notably reduced in the osteogenic areas of the retinoic acid\u2010 treated palates. Our data suggest that retinoic acid impairs palate fusion and bone formation by upregulation of WNT signaling.<\/jats:p>","DOI":"10.1111\/eos.12899","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T03:43:48Z","timestamp":1666928628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Retinoic acid effects on in vitro palatal fusion and WNT signaling"],"prefix":"10.1111","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-2214","authenticated-orcid":false,"given":"Laury Amelia","family":"Roa Fuentes","sequence":"first","affiliation":[{"name":"Department of Orthodontics and Craniofacial Biology Radboud Institute for Molecular Life Sciences Radboud university medical center  Nijmegen The Netherlands"},{"name":"MERLN Institute for Technology\u2010Inspired Regenerative Medicine Department of Instructive Biomaterial Engineering (IBE) Maastricht University  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