Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse.
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 beta-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.
Murashima-Suginami
Akiko
A
Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Takahashi
Katsu
K
Sakata
Tomoko
T
Tsukamoto
Hiroko
H
Sugai
Manabu
M
Yanagita
Motoko
M
Shimizu
Akira
A
Sakurai
Takeshi
T
Slavkin
Harold C
HC
Bessho
Kazuhisa
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D007180:Incisor / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction; D014096:Tooth, Supernumerary / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C483887:Sostdc1 protein, mouse; D051153:Wnt Proteins