Wnt signal plays a role in formation of mineralized tissue in dental pulp.

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Wnt signaling is important in organogenesis. Among differentially expressed Wnts during tooth development, only Wnt5a is expressed in the dental mesenchyme. The present study aims to clarify the expression pattern of Wnt5a in developing tooth germs and the role of Wnt5a in the regulation of tooth size by treatment of exogenous WNT5A with/without apoptosis inhibitor on in vitro tooth germs combined with the transplantation into the kidney capsule. Wnt5a was expressed in both the dental epithelium and mesenchyme during E14-17 overlapped partly with both Shh and Bmp4 expressions. Moreover, WNT5A retarded the development of tooth germs by inducing cell death severely in the non-dental epithelium and mesenchyme, but not severely in the dental region, where the epithelial-mesenchymal gene interactions among Wnt5a, Fgf10, Bmp4, and Shh might partly rescue the cell death in the WNT5A-treated tooth germ. Taken together, WNT5A-induced cell death inhibited overall development of tooth germ, resulting in smaller size of teeth with blunter cusps after tooth germ transplantation. Thus, Wnt5a is suggestive to be involved in regulating cell death in non-dental regions, while Wnt5a in the dental region acts as a regulator of other genes to rescue the cell death of tooth germ.