title: Wnt5a plays a crucial role in determining tooth size during murine tooth development.
abstract: We have previously demonstrated that tooth size is determined by dental mesenchymal factors. Exogenous bone morphogenetic protein (BMP)4, Noggin, fibroblast growth factor (FGF)3 and FGF10 have no effect on tooth size, despite the expressions of Bmp2, Bmp4, Fgf3, Fgf10 and Lef1 in the dental mesenchyme. Among the wingless (Wnt) genes that are differentially expressed during tooth development, only Wnt5a is expressed in the dental mesenchyme. The aims of the present study were to clarify the expression pattern of Wnt5a in developing tooth germs and the role of Wnt5a in the regulation of tooth size by treatment with exogenous WNT5A with/without an apoptosis inhibitor on in vitro tooth germs combined with transplantation into kidney capsules. Wnt5a was intensely expressed in both the dental epithelium and mesenchyme during embryonic days 14-17, overlapping partly with the expressions of both Shh and Bmp4. Moreover, WNT5A retarded the development of tooth germs by markedly inducing cell death in the non-dental epithelium and mesenchyme but not widely in the dental region, where the epithelial-mesenchymal gene interactions among Wnt5a, Fgf10, Bmp4 and Shh might partly rescue the cells from death in the WNT5A-treated tooth germ. Together, these results indicate that WNT5A-induced cell death inhibited the overall development of the tooth germ, resulting in smaller teeth with blunter cusps after tooth-germ transplantation. Thus, it is suggested that Wnt5a is involved in regulating cell death in non-dental regions, while in the dental region it acts as a regulator of other genes that rescue tooth germs from cell death.
authors: Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Oral Science Research Center, College of Dentistry, Brain Korea 21 Project for Medical Science, Yonsei University, Seoul.
authors: Jinglei
authors: J
authors: Cai
authors: Noriko
authors: N
authors: Mutoh
authors: Jeong-Oh
authors: JO
authors: Shin
authors: Nobuyuki
authors: N
authors: Tani-Ishii
authors: Hayato
authors: H
authors: Ohshima
authors: Sung-Won
authors: SW
authors: Cho
authors: Han-Sung
authors: HS
authors: Jung
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay; D019521:Body Patterning / Q000187:drug effects; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002021:Buffers; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D009929:Organ Size / Q000187:drug effects; D014070:Tooth / Q000033:anatomy & histology* / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D014083:Tooth Germ / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000071818:Wnt-5a Protein
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D055415:Bone Morphogenetic Protein 4; D002021:Buffers; D051526:Fibroblast Growth Factor 10; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone