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Published 6 December 2004. doi:10.1083/jcb.200409077
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 5, 973-983
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Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts

Satoshi Fukumoto1,2, Takayoshi Kiba1, Bradford Hall1, Noriyuki Iehara1, Takashi Nakamura1, Glenn Longenecker1, Paul H. Krebsbach3, Antonio Nanci4, Ashok B. Kulkarni1, and Yoshihiko Yamada1

1 Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
2 Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
3 Department of Oral Medicine, Pathology and Oncology, School of Dentistry, The University of Michigan, Ann Arbor, MI 48109
4 Department of Stomatology, Faculty of Dentistry, Université de Montréal, Montreal, QC, Canada H3C 3J7

Correspondence to Yoshihiko Yamada: yoshi.yamada{at}nih.gov

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.

Abbreviations used in this paper: E, embryonic day; ES, embryonic stem; P, postnatal day; SEM, scanning electron microscopic.


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