G protein-coupled receptor () is required for enamel mineralization mediated by ameloblasts.

Dental enamel, the hardest tissue in the human body, is derived from dental epithelial cell ameloblast-secreted enamel matrices. Enamel mineralization occurs in a strictly synchronized manner along with ameloblast maturation in association with ion transport and pH balance, and any disruption of these processes results in enamel hypomineralization. G protein-coupled receptors (GPCRs) function as transducers of external signals by activating associated G proteins and regulate cellular physiology. Tissue-specific GPCRs play important roles in organ development, although their activities in tooth development remain poorly understood. The present results show that the adhesion GPCR () is highly and preferentially expressed in mature ameloblasts and plays a crucial role during enamel mineralization. To investigate the function of , knockout (-KO) mice were created and found to develop hypomineralized enamel, with a larger acidic area because of the dysregulation of ion composition. Transcriptomic analysis also revealed that deletion of disrupted pH homeostasis and ion transport processes in enamel formation. In addition, analyses using the dental epithelial cell line cervical loop-derived dental epithelial (CLDE) cell demonstrated that is indispensable for the expression of carbonic anhydrase 6 (), which has a critical role in enamel mineralization. Furthermore, an acidic condition induced expression under the regulation of in CLDE cells. Thus, we concluded that plays an important role in enamel mineralization via regulation of expression in ameloblasts. The present findings indicate a novel function of in ectodermal organ development and clarify the molecular mechanism of enamel formation.