{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:27:10Z","timestamp":1789046830548,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,8,23]],"date-time":"2012-08-23T00:00:00Z","timestamp":1345680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology of the Cell"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background information<\/jats:title><jats:p>Previous studies have indicated that over\u2010activation of the wingless interaction site (Wnt)\/\u03b2\u2010catenin signalling pathway has important implications for tooth development, at the level of cell differentiation and morphology, as well as for the production of supernumerary teeth. Here, we provide evidence for a crucial role of this signalling pathway during the stage of tooth morphogenesis. We have developed an <jats:italic>in vitro<\/jats:italic> model consisting of 14.5\u2010day\u2010old mouse embryo first molars, in which the Wnt pathway is overactivated by the glycogen synthase kinase\u20103 inhibitor 6\u2010bromoindirubin\u20103\u2032\u2010oxime (BIO; 20 \u00b5M).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that over\u2010activation of the Wnt\/\u03b2\u2010catenin pathway delayed the differentiation and growth of the inner dental epithelium. In addition, in contrast to controls in which Nestin protein expression was restricted to differentiated odontoblasts, in BIO\u2010treated molars, Nestin expression spread through sub\u2010odontoblastic cellular layers. This alteration appears to be related to: (i) the over\u2010expression of <jats:italic>Bmp4<\/jats:italic> in the same region, (ii) the delay in odontoblast precursor cell differentiation and (iii) increased proliferation of mesenchymal cells. Furthermore, treatments longer than 6 days induced the malformation of typical dental structures and led to a total lack of cell differentiation. Finally, over\u2010activation of the Wnt route during odontogenesis resulted in adult teeth which presented altered size, morphology and mineralisation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that Wnt\/\u03b2\u2010catenin over\u2010activation during tooth morphogenesis is sufficient to cause dramatic alterations in the adult tooth, by delaying cellular differentiation and stimulating proliferation of the dental mesenchyme of developing teeth.<\/jats:p><\/jats:sec>","DOI":"10.1111\/boc.201100075","type":"journal-article","created":{"date-parts":[[2012,6,4]],"date-time":"2012-06-04T17:17:08Z","timestamp":1338830228000},"page":"603-617","source":"Crossref","is-referenced-by-count":17,"title":["Enhanced Wnt\/\u03b2\u2010catenin signalling during tooth morphogenesis impedes cell differentiation and leads to alterations in the structure and mineralisation of the adult 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