Wnt5a plays a crucial role in determining tooth size during murine tooth development
Copyright policy )Wnt5a plays a crucial role in determining tooth size during murine tooth development
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.
- Yonsei University Korea (Republic of)
- Niigata University Japan
- University of Hong Kong China (People's Republic of)
- Yonsei University Health System Korea (Republic of)
- Yonsei University Medical Library Korea (Republic of)
670, Amino Acid Chloromethyl Ketones/pharmacology, Developmental/drug effects, Apoptosis, Bone Morphogenetic Protein 4, Fibroblast Growth Factor 10 - Genetics - Metabolism, Amino Acid Chloromethyl Ketones, Tooth transplantation, Mice, Models, Tooth/anatomy & histology*, Tooth Germ/embryology, Tooth Germ - Cytology - Drug Effects - Embryology - Metabolism, Body Patterning/drug effects, Mice (ICR), Mice, Inbred Icr, Mice, Inbred ICR, Body Patterning - Drug Effects, Gene Expression Regulation, Developmental, Organ Size, Inbred ICR, Inbred Icr, Biological Assay, Tooth Germ/cytology, Fibroblast Growth Factor 10/genetics, Wnt Proteins/metabolism*, Apoptosis - Drug Effects, Tooth/embryology*, 610, Wnt Proteins/pharmacology, Tooth - Anatomy & Histology - Cytology - Drug Effects - Embryology, Buffers, Models, Biological, Wnt-5a Protein, 617, Animals, Organ Size/drug effects, Gene Expression Regulation, Developmental - Drug Effects, Amino Acid Chloromethyl Ketones - Pharmacology, Fibroblast Growth Factor 10/metabolism, Bone Morphogenetic Protein 4/genetics, Wnt Proteins/genetics, Body Patterning, Organ Size - Drug Effects, Apoptosis/drug effects, Tooth Germ, Tooth/cytology, Bone Morphogenetic Protein 4 - Genetics - Metabolism, Biological, Tooth/drug effects, Wnt proteins, Wnt Proteins, Gene Expression Regulation, Bone Morphogenetic Protein 4/metabolism, Developmental - Drug Effects, Wnt Proteins - Genetics - Metabolism - Pharmacology, Tooth Germ/metabolism, Tooth Germ/drug effects, Fibroblast Growth Factor 10, Tooth
670, Amino Acid Chloromethyl Ketones/pharmacology, Developmental/drug effects, Apoptosis, Bone Morphogenetic Protein 4, Fibroblast Growth Factor 10 - Genetics - Metabolism, Amino Acid Chloromethyl Ketones, Tooth transplantation, Mice, Models, Tooth/anatomy & histology*, Tooth Germ/embryology, Tooth Germ - Cytology - Drug Effects - Embryology - Metabolism, Body Patterning/drug effects, Mice (ICR), Mice, Inbred Icr, Mice, Inbred ICR, Body Patterning - Drug Effects, Gene Expression Regulation, Developmental, Organ Size, Inbred ICR, Inbred Icr, Biological Assay, Tooth Germ/cytology, Fibroblast Growth Factor 10/genetics, Wnt Proteins/metabolism*, Apoptosis - Drug Effects, Tooth/embryology*, 610, Wnt Proteins/pharmacology, Tooth - Anatomy & Histology - Cytology - Drug Effects - Embryology, Buffers, Models, Biological, Wnt-5a Protein, 617, Animals, Organ Size/drug effects, Gene Expression Regulation, Developmental - Drug Effects, Amino Acid Chloromethyl Ketones - Pharmacology, Fibroblast Growth Factor 10/metabolism, Bone Morphogenetic Protein 4/genetics, Wnt Proteins/genetics, Body Patterning, Organ Size - Drug Effects, Apoptosis/drug effects, Tooth Germ, Tooth/cytology, Bone Morphogenetic Protein 4 - Genetics - Metabolism, Biological, Tooth/drug effects, Wnt proteins, Wnt Proteins, Gene Expression Regulation, Bone Morphogenetic Protein 4/metabolism, Developmental - Drug Effects, Wnt Proteins - Genetics - Metabolism - Pharmacology, Tooth Germ/metabolism, Tooth Germ/drug effects, Fibroblast Growth Factor 10, Tooth
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