{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T09:49:34Z","timestamp":1774000174012,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"\n Introduction<\/jats:title>\n Mammalian palates are composed of the anterior hard palate and the posterior soft palate. However, the correlation of the genesis, pattern formation, and morphogenesis between the hard and soft palates remains elusive.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this study, we explicated the complicated palatal defects in\n Osr2-cre<\/jats:italic>\n \n KI<\/jats:italic>\n <\/jats:sup>\n ;Ctnnb1<\/jats:italic>\n \n ex3f<\/jats:italic>\n <\/jats:sup>\n mice, in which canonical Wnt activity was persistent due to constitutively active \u03b2-catenin in the palatal mesenchyme.\n Osr2-cre<\/jats:italic>\n \n KI<\/jats:italic>\n <\/jats:sup>\n ;Ctnnb1<\/jats:italic>\n \n ex3f<\/jats:italic>\n <\/jats:sup>\n palates displayed an ectopic mesenchymal condensation extending from the proximal\u2013posterior area to the distal\u2013anterior area, along with impaired osteogenesis and agenesis of soft palate.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Immunohistochemistry showed the overlapping active canonical Wnt domain with the ectopic mesenchymal condensation, indicating that the condensation was induced by persistent canonical Wnt signaling.\n Wnt5a<\/jats:italic>\n , a chemokine that induces posterior\u2013anterior migration of palatal mesenchymal cells, was activated in the anterior and middle palatal mesenchyme of\n Osr2-cre<\/jats:italic>\n \n KI<\/jats:italic>\n <\/jats:sup>\n ;Ctnnb1<\/jats:italic>\n \n ex3f<\/jats:italic>\n <\/jats:sup>\n mice. Exogenous supplementation of Wnt5a into wild-type (WT) palates recapitulated the mesenchymal condensation. These findings indicate that the persistent canonical Wnt signaling in the palatal mesenchyme extended\n Wnt5a<\/jats:italic>\n expression, which enforced posterior mesenchymal migration toward the anterior to form the convoluted condensation, thereby impairing the genesis of the soft palate in\n Osr2-cre<\/jats:italic>\n \n KI<\/jats:italic>\n <\/jats:sup>\n ;Ctnnb1<\/jats:italic>\n \n ex3f<\/jats:italic>\n <\/jats:sup>\n mice. Moreover, the medially osteogenic markers\n Sox9<\/jats:italic>\n ,\n Runx2<\/jats:italic>\n , and\n Osx<\/jats:italic>\n ; the laterally\n Shh<\/jats:italic>\n ,\n Foxf1<\/jats:italic>\n , and\n Fgf10<\/jats:italic>\n ; and another Wnt inhibitor,\n Sfrp2<\/jats:italic>\n , were significantly reduced or even diminished in\n Osr2-cre<\/jats:italic>\n \n KI<\/jats:italic>\n <\/jats:sup>\n ;Ctnnb1<\/jats:italic>\n \n ex3f<\/jats:italic>\n <\/jats:sup>\n palatal shelves. In contrast, the condensed\n Osr2-cre<\/jats:italic>\n \n KI<\/jats:italic>\n <\/jats:sup>\n ;Ctnnb1<\/jats:italic>\n \n ex3f<\/jats:italic>\n <\/jats:sup>\n palatal mesenchyme displayed the medial markers Dlx5 and p-Smad1\/5\/8, along with the fibrosis\/dermal markers \u0251-SMA and Tbx15. The Wnt and TGF-\u03b2\/BMP inhibitors\n Ectodin<\/jats:italic>\n and\n Noggin<\/jats:italic>\n were also ectopically activated in the palatal epithelium overlying the condensed mesenchyme\n Osr2-cre<\/jats:italic>\n \n KI<\/jats:italic>\n <\/jats:sup>\n ;Ctnnb1<\/jats:italic>\n \n ex3f<\/jats:italic>\n <\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n These findings indicate a transition of palatal mesenchymal cells from an osteogenic fate into fibrosis commitment, along with disrupted mediolateral patterning of the palatal shelves due to persistent canonical Wnt activity. Our study provides molecular clues that fine-tuning the mesenchymal canonical Wnt activity and Wnt5a-directed cell migration correlates with the morphogenesis of hard palates and the genesis of soft palates.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcell.2026.1740081","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T06:38:59Z","timestamp":1773988739000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Persistent Wnt\/\u03b2-catenin signaling disables soft palatogenesis and palatal osteogenesis by inducing mesenchymal condensation"],"prefix":"10.3389","volume":"14","author":[{"given":"Biying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, Dalian Medical University School of Stomatology","place":["Dalian, China"]},{"name":"Department of Periodontology and Oral Mucosal Diseases, General Hospital of Chinese People\u2019s Liberal 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