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Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse |
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| Authors: | Murashima-Suginami Akiko Takahashi Katsu Sakata Tomoko Tsukamoto Hiroko Sugai Manabu Yanagita Motoko Shimizu Akira Sakurai Takeshi Slavkin Harold C Bessho Kazuhisa |
| Institution: | a Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan b Department of Clinical Genetics Unit, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan c COE Formation for Genomic Analysis of Disease Model Animals with Multiple Genetic Alterations, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan d Yanagisawa Orphan Receptor Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Agency, Tokyo 135-0064, Japan e Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan f Dean’s Office, Faculty of Dentistry, University of Southern California, 925 West 34th Street, Suite 203, Los Angeles, CA 90089-0641, USA |
| Abstract: | Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist, and also modulates Wnt signaling. We previously reported that USAG-1 deficient mice have supernumerary teeth. The supernumerary maxillary incisor appears to form as a result of the successive development of the rudimentary upper incisor. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. We confirmed that BMPs were expressed in both the epithelium and mesenchyme of the rudimentary incisor at E14 and E15. BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced. Wnt signaling as demonstrated by the nuclear localization of β-catenin was also up-regulated. Inhibition of BMP signaling rescues supernumerary tooth formation in E15 incisor explant culture. Based upon these results, we conclude that enhanced BMP signaling results in supernumerary teeth and BMP signaling was modulated by Wnt signaling in the USAG-1 deficient mouse model. |
| Keywords: | USAG-1 BMP signaling Supernumerary teeth |
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