Essential Role of mTOR Signaling in Enamel Organ Development

Objectives: The objectives of this research are to determine the degree of mTOR expression in successive stages of tooth development and to understand the pathological effects of mTOR knockout on enamel organ development.
Methods: Tissue-specific mTOR knockout models were created using the Keratin14–Cre and floxed mTOR mouse strains. Expression of mTOR in the enamel organ and mesenchymal tissue was visualized through immunofluorescence using a phospho-mTOR antibody. Histologic examination was conducted using Hematoxylin and Eosin staining. All quantitative data were analyzed by two-tailed t-test.
Results: Expression analysis revealed that mTOR is expressed in both the enamel organ and mesenchyme during the bud stage of enamel organ development but is primarily expressed in the enamel organ during later stages. Deletion of mTOR in dental epithelia causes defective development of the enamel organ. At birth, teeth showed altered shape: molars were smaller with atypical tooth cusps, and incisors were shorter with blunted tips. Histological examination of tooth germs revealed disruption of the stellate reticulum layer, cyst formation in the enamel organ, and defective differentiation of ameloblasts.
Conclusions: mTOR signaling plays a critical role in enamel organ development, and disruption of this pathway causes tooth malformation. This pathogenesis is similar to that seen in tooth hypoplasia and dentigerous cysts. Dysregulation of mTOR may be an underlying cause of human tooth malformation, and understanding this pathway could bring researchers and clinicians closer to treating these disease processes.