Abstract
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 Statement
The authors have declared no competing interest.
Footnotes
This manuscript is available as a preprint on non-commercial server bioRxiv: https://doi.org/10.1101/2020.09.16.299388.
Disclosure page
Conflicts of interest The authors declare no conflicts of interest.
Data Availability Statement All the data are available within the article or its supplementary materials.
The whole article has been revised.
