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Wnt5a plays a crucial role in determining tooth size during murine tooth development

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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.

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Authors and Affiliations

  1. 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, 250 Seongsanno, Seodaemoon-Gu, Seoul, 120-752, Korea

    Jinglei Cai, Jeong-Oh Shin, Sung-Won Cho & Han-Sung Jung

  2. StemCell and Cancer Biology Group, Key Laboratory of Regenerative Biology, South China Institute for StemCell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510663, China

    Jinglei Cai

  3. Division of Endodontics, Department of Oral Medicine, Kanagawa Dental College, Yokosuka, Japan

    Noriko Mutoh & Nobuyuki Tani-Ishii

  4. Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Hayato Ohshima

Authors
  1. Jinglei Cai
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  2. Noriko Mutoh
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  3. Jeong-Oh Shin
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  4. Nobuyuki Tani-Ishii
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  5. Hayato Ohshima
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  6. Sung-Won Cho
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  7. Han-Sung Jung
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Corresponding author

Correspondence to Han-Sung Jung.

Additional information

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MEST) (No. 2011-0027790)

Jinglei Cai and Noriko Mutoh contributed equality to this work.

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Supplemental figure 1

Apoptosis assay of exogenous WNT5A (100 μg/ml). Hematoxylin and eosin (a, b, e, f, i, j) and TUNEL (c, d, g, h, k, l) staining in frontal sections of tooth germs cultured with PBS- (a, c, e, g, i, k) and WNT5A-soaked (b, d, f, h, j, l) beads (*) during 12 (a–d), 24 (e–h), and 48 h (i–l). c, g, k A few TUNEL-positive spots are located in the epithelium and mesenchyme of control explants. d, h, l TUNEL-labeled mesenchymal cells are observed in the area around the beads in a WNT5A-treated tooth germ. However, few TUNEL-labeled cells are detected in the dental region (arrows or arrowheads). (JPG 85 KB)

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Cai, J., Mutoh, N., Shin, JO. et al. Wnt5a plays a crucial role in determining tooth size during murine tooth development. Cell Tissue Res 345, 367–377 (2011). https://doi.org/10.1007/s00441-011-1224-4

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  • DOI: https://doi.org/10.1007/s00441-011-1224-4

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