Rudiment incisors survive and erupt as supernumerary teeth as a result of USAG-1 abrogation

The term “supernumerary teeth” describes production of more than the normal number of teeth in the primary or permanent dentitions. Their aetiology is not understood. Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist that plays important roles in the local regulation of BMP signaling by binding and neutralizing BMP activities [M. Yanagita, BMP antagonists: their roles in development and involvement in pathophysiology, Cytokine Growth Factor Rev. 16 (2005) 309-317], and also serves as a modulator of Wnt signaling [N. Itasaki, C.M. Jones, S. Mercurio, A. Rowe, P.M. Domingos, J.C. Smith, R. Krumlauf, Wise, a context-dependent activator and inhibitor of Wnt signaling, Development 130 (2003) 4295-4305]. We report here 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 tooth. We confirmed that the USAG-1 expression is localized to the epithelium and mesenchyme of the rudimentary maxillary incisor tooth organ formation. USAG-1 abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. Based upon these results, we conclude that USAG-1 controls the number of teeth in the maxillary incisor region by regulating apoptosis.