Follistatin controls the number of murine teeth by limiting TGF-β signaling
Shicheng Zhu,
Suman Huo,
Zhongzheng Wang,
Caiyan Huang,
Chuanxu Li,
Hanjing Song,
Xueqin Yang,
Rui He,
Cheng Ding,
Mengsheng Qiu,
Xiao-Jing Zhu
Affiliations
Shicheng Zhu
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
Suman Huo
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
Zhongzheng Wang
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
Caiyan Huang
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
Chuanxu Li
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
Hanjing Song
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
Xueqin Yang
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
Rui He
The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang 310015, China
Cheng Ding
The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang 310015, China
Mengsheng Qiu
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
Xiao-Jing Zhu
College of Life and Environmental Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Corresponding author
Summary: 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 Fst, encoding an antagonist for the transforming growth factor β (TGF-β) signaling pathway, in both oral epithelium and mesenchyme of mice (FstCKO) 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. Fst-deficiency greatly activated TGF-β signaling in developing maxillary incisor teeth, associated with increased epithelium cell proliferation. Moreover, FstCKO teeth exhibited increased expression of Tbx1, Sp6, and Sox2, which were identified as direct targets of TGF-β/SMAD2 signaling. Finally, we show that upregulation of Tbx1 in response to Fst-deficiency was largely responsible for the formation of extra teeth in FstCKO mice. Taken together, our investigation indicates a novel role for Fst in controlling murine tooth number by restricting TGF-β signaling.
