Gadd45g regulates dental epithelial cell proliferation through p38 MAPK-mediated p21 expression.

Ectodermal organs, such as teeth, hair follicles, and mammary glands, arise from their respective germs through epithelial–mesenchymal interactions during organogenesis. Growth arrest and DNA damage-inducible gene gamma (Gadd45g) have been shown to play important roles in various biological processes, such as stress responses, cell differentiation, and tumor suppression, through the regulation of cell proliferation and gene expression. We found that Gadd45g was expressed in enamel knots, which orchestrate tooth germ development as epithelial signaling centers. Gadd45g induced the expression of p21 and inhibited the proliferation of dental epithelial cells. The up-regulation of p21 expression was regulated by Gadd45g-mediated activation of the p38 MAPK pathway. Thus, our results suggest that Gadd45g is involved in the regulation of p21-mediated epithelial cell proliferation through the p38 MAPK pathway during tooth organ development.