Hepatocyte growth factor is involved in the morphogenesis of tooth germ in murine molars

Makoto J. Tabata, Kenji Kim, Ji Guang Liu, Kazuo Yamashita, Tatsushi Matsumura, Joji Kato, Masahiro Iwamoto, Satoshi Wakisaka, Kunio Matsumoto, Toshikazu Nakamura, Masayoshi Kumegawa, Kojiro Kurisu

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Abstract

The patterns of gene expression for hepatocyte growth factor (HGF) and its receptor, c-Met, were revealed in the tooth germ of rat mandibular molars using RT-PCR. In situ hybridization demonstrated that the HGF gene was expressed only in the cells of the dental papilla of the tooth germ in vivo. The characteristic temporospatial distribution of HGF and c-Met during germ development was revealed using immunohistochemical studies in vivo. In order to demonstrate the functional role played by HGF in tooth development, HGF translation arrest by antisense phosphorothioate oligodeoxynucleotide (ODN) was carried out in vitro. In the control experiment, explants of tooth germs from embryonic 14 day mice were cultured in a modification of Trowell's system under serum-free and chemically defined conditions for two weeks. Other explants were cultured with 15mer antisense or sense ODN targeted to the HGF mRNA. Both the control and the sense-treated explants showed normal histological structure, as observed in vivo. On the other hand, antisense-treated explants exhibited an abnormal structure in which the enamel organs were surrounded by a thin layer of dentin and dental papilla, appearing 'inside-out' compared to the control and sense-treated explants, although the cytodifferentiation of ameloblasts and odontoblasts was not inhibited. The explants treated with recombinant human HGF combined with antisense ODN showed normal development, indicating that exogenous HGF rescued the explants from the abnormal structure caused by antisense ODN. The findings of a BrdU incorporation experiment suggested that the imbalance between the proliferation activity of the inner enamel epithelium and that of the dental papilla caused by HGF translation arrest results in the abnormal structure of the tooth germ. These results indicate that HGF is involved in the morphogenesis of the murine molar.

Original languageEnglish
Pages (from-to)1243-1251
Number of pages9
JournalDevelopment
Volume122
Issue number4
Publication statusPublished - Apr 1 1996
Externally publishedYes

Keywords

  • Antisense oligodeoxynucleotide
  • Hepatocyte growth factor (HGF/SF)
  • Murine tooth development
  • Organ culture of tooth germ
  • c-met

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Tabata, M. J., Kim, K., Liu, J. G., Yamashita, K., Matsumura, T., Kato, J., Iwamoto, M., Wakisaka, S., Matsumoto, K., Nakamura, T., Kumegawa, M., & Kurisu, K. (1996). Hepatocyte growth factor is involved in the morphogenesis of tooth germ in murine molars. Development, 122(4), 1243-1251.