Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts

Satoshi Fukumoto, Takayoshi Kiba, Bradford Hall, Noriyuki Iehara, Takashi Nakamura, Glenn Longenecker, Paul H. Krebsbach, Antonio Nanci, Ashok B. Kulkarni, Yoshihiko Yamada

Research output: Contribution to journalArticlepeer-review

272 Citations (Scopus)

Abstract

Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin. During this process, epithelial cells differentiate into enamel-secreting ameloblasts. Ameloblastin, an enamel matrix protein, is expressed by differentiating ameloblasts. Here, we report the creation of ameloblastin-null mice, which developed severe enamel hypoplasia. In mutant tooth, the dental epithelium differentiated into enamel-secreting ameloblasts, but the cells were detached from the matrix and subsequently lost cell polarity, resumed proliferation, and formed multicell layers. Expression of Msx2, p27, and p75 were deregulated in mutant ameloblasts, the phenotypes of which were reversed to undifferentiated epithelium. We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation. The mutant mice developed an odontogenic tumor of dental epithelium origin. Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretory stage ameloblasts by binding to ameloblasts and inhibiting proliferation.

Original languageEnglish
Pages (from-to)973-983
Number of pages11
JournalJournal of Cell Biology
Volume167
Issue number5
DOIs
Publication statusPublished - 2004 Dec 5
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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