RT Journal Article SR Electronic T1 FGF8-mediated signaling regulates tooth developmental pace and size during odontogenesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.09.16.299388 DO 10.1101/2020.09.16.299388 A1 Lin, Chensheng A1 Ruan, Ningsheng A1 Li, Linjun A1 Chen, Yibin A1 Hu, Xiaoxiao A1 Chen, YiPing A1 Hu, Xuefeng A1 Zhang, Yanding YR 2021 UL http://biorxiv.org/content/early/2021/02/19/2020.09.16.299388.abstract AB The developing human and mouse teeth constitute an ideal model system to study the regulatory mechanism underlying organ growth control due to the fact that their teeth share highly conserved and well-characterized developmental processes and their developmental tempo and size vary notably. In the current study, we manipulated heterogenous recombination between human and mouse dental tissues and demonstrate that the dental mesenchyme dominates the tooth developmental tempo and size and FGF8 could be a critical player during this developmental process. Forced activation of FGF8 signaling in the dental mesenchyme of mice promoted cell proliferation, prevented cell apoptosis via p38 and perhaps PI3K-Akt intracellular signaling, and impelled the transition of the cell cycle from G1- to S-phase in the tooth germ, resulting in the slowdown of the tooth developmental pace and the enlargement of the tooth size. Our results provide compelling evidence that extrinsic signals can profoundly affect tooth developmental tempo and size and the dental mesenchymal FGF8 could be a pivotal factor in controlling developmental pace and size in a non-cell-autonomous manner during mammalian odontogenesis.Competing Interest StatementThe authors have declared no competing interest.