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

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.

Neurotrophic Factor Neurotrophin-4 Regulates Ameloblastin Expression via Full-length TrkB

“…We found that p75 was expressed in an undifferentiated dental epithelial cell line but was not detectable in the tooth germ. It was reported that in incisors, p75 is expressed in the inner dental epithelium but is completely absent in differentiated ameloblasts (6). Further, the possibility of epithelial-mesenchymal communication within the intact tooth germ, whereas there is complete absence of those effects in the individual cells cultures, may be at the root of the differences of p75 expression between tooth germ and dental epithelial cell cultures.…”

“…Ambn, also known as amelin or sheathlin, is a tooth-specific glycoprotein that represents the most abundant non-Amel enamel matrix protein. We previously created Ambn-null mice, which develop severe enamel hypoplasia in which ameloblasts detached from the matrix, lost cell polarity, resumed proliferation, and formed multiple cell layers (6). These results suggest that Ambn is essential for ameloblast differentiation and enamel formation.…”

Altering Biomineralization by Protein Design

“…Amelogenin protein lacks canonical integrin binding motifs; however, another rodent enamel protein, ameloblastin, does contain an RGD motif and has been shown to be involved with attachment of the ameloblasts to the matrix (29,30). Therefore, we used anti-integrin ␣6 antibodies (31) to examine the distribution of integrin molecules localized to the Tomes' processes.…”

FAM20C Plays an Essential Role in the Formation of Murine Teeth

“…The amelogenesis process is divided into the presecretory stage, secretory stage, and maturation stage, with marker genes expressed at each phase. Over the past decade, mouse models engineered for the loss-of-function analyses of AMEL (29), AMBN (30,31), ENAM (32), MMP20 (33), and KLK4 (34) have been reported. Among these engineered models, the enamel defects of Ambn KO and Enam KO mice (35) were very similar to those of the Fam20C KO mice.…”