Follistatin controls the number of murine teeth by limiting TGF-β signaling.

Supernumerary teeth are common developmental anomalies of dentition. However, the factors and mechanisms driving their formation remain largely unknown. Here, we report that conditional knockout of , encoding an antagonist for the transforming growth factor β (TGF-β) signaling pathway, in both oral epithelium and mesenchyme of mice ( ) led to supernumerary upper incisor teeth, arising from the lingual dental epithelium of the native teeth and preceded by an enlarged and split lingual cervical loop. deficiency greatly activated TGF-β signaling in developing maxillary incisor teeth, associated with increased epithelium cell proliferation. Moreover, teeth exhibited increased expression of , , and , which were identified as direct targets of TGF-β/SMAD2 signaling. Finally, we show that upregulation of in response to -deficiency was largely responsible for the formation of extra teeth in mice. Taken together, our investigation indicates a novel role for in controlling murine tooth number by restricting TGF-β signaling.