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

Fukumoto S, Kiba T, Hall B, Iehara N, Nakamura T, Longenecker G, Krebsbach PH, Nanci A, Kulkarni AB, Yamada Y - J. Cell Biol. (2004)

Bottom Line: Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin.We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation.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.

View Article: PubMed Central - PubMed

Affiliation: Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.

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- 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.

Show MeSH

Related in: MedlinePlus

Expression of tooth markers in mutant mice. (A) mRNA expression in P3 mandibular first molars by RT-PCR. (B) Immunostaining of tooth marker proteins, ameloblastin, amelogenin, tuftelin, enamelin, and dentin sialoprotein (DSP) in P3 molars. There is no ameloblastin staining in mutant molars. (C) Silver staining of total lysates from P3 mandibular molars from two different heterozygous and mutant mice separated by SDS-PAGE. Arrows indicate the amelogenin protein and their cleaved derivatives. (D) Western blot analysis of amelogenin in P3 mandibular first molars.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172447&req=5

fig5: Expression of tooth markers in mutant mice. (A) mRNA expression in P3 mandibular first molars by RT-PCR. (B) Immunostaining of tooth marker proteins, ameloblastin, amelogenin, tuftelin, enamelin, and dentin sialoprotein (DSP) in P3 molars. There is no ameloblastin staining in mutant molars. (C) Silver staining of total lysates from P3 mandibular molars from two different heterozygous and mutant mice separated by SDS-PAGE. Arrows indicate the amelogenin protein and their cleaved derivatives. (D) Western blot analysis of amelogenin in P3 mandibular first molars.

Mentions: To better characterize and gain insight into the mechanism of the abnormalities of ameloblasts in mutant mice, we examined the expression of regulatory factors and tooth marker proteins (Figs. 4 and 5). It was shown that the homeobox-containing transcription factor Msx2 was expressed in undifferentiated ameloblasts but was down-regulated in secretory stage ameloblasts (Maas and Bei, 1997). P3 Ambn+/− ameloblasts expressed the Msx2 protein but its expression was diminished in P7 ameloblasts (Fig. 4). In mutant Amb−/− mice, Msx2 was expressed at P3 ameloblasts, similar to P3 Ambn+/− tooth. However, Msx2 was still expressed in a multiple cell layer of ameloblasts of P7 mutant tooth in contrast to P7 control tooth. p27, a Cdk inhibitor, was strongly expressed in P7 ameloblasts compared with P3 ameloblasts in Ambn+/− tooth (Bloch-Zupan et al., 1998), whereas its expression remained weak in P7 ameloblasts of mutant tooth. p75, a member of the TNF receptor family, was expressed in P3 Ambn+/− ameloblasts, and its expression was diminished at P7 (Mitsiadis et al., 1993). In contrast, p75 was expressed strongly in ameloblasts in P7 mutant tooth. Similar expression patterns of these proteins were observed in incisors containing all differentiation stages of the dental epithelium (unpublished data). Immunostaining of p27 was positive in immediate-early Ambn−/− ameloblasts, but it was reduced in the multicell layer of early secretory ameloblasts (unpublished data). This suggested that the proliferation of ameloblasts stopped at the immediate-early secretory stage but resumed from the early secretory stage. These results suggest that in mutant tooth, Ambn−/− ameloblasts regain certain early phenotypes of undifferentiated dental epithelium, when cells detach from the matrix and form a multicell layer.


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

Fukumoto S, Kiba T, Hall B, Iehara N, Nakamura T, Longenecker G, Krebsbach PH, Nanci A, Kulkarni AB, Yamada Y - J. Cell Biol. (2004)

Expression of tooth markers in mutant mice. (A) mRNA expression in P3 mandibular first molars by RT-PCR. (B) Immunostaining of tooth marker proteins, ameloblastin, amelogenin, tuftelin, enamelin, and dentin sialoprotein (DSP) in P3 molars. There is no ameloblastin staining in mutant molars. (C) Silver staining of total lysates from P3 mandibular molars from two different heterozygous and mutant mice separated by SDS-PAGE. Arrows indicate the amelogenin protein and their cleaved derivatives. (D) Western blot analysis of amelogenin in P3 mandibular first molars.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172447&req=5

fig5: Expression of tooth markers in mutant mice. (A) mRNA expression in P3 mandibular first molars by RT-PCR. (B) Immunostaining of tooth marker proteins, ameloblastin, amelogenin, tuftelin, enamelin, and dentin sialoprotein (DSP) in P3 molars. There is no ameloblastin staining in mutant molars. (C) Silver staining of total lysates from P3 mandibular molars from two different heterozygous and mutant mice separated by SDS-PAGE. Arrows indicate the amelogenin protein and their cleaved derivatives. (D) Western blot analysis of amelogenin in P3 mandibular first molars.
Mentions: To better characterize and gain insight into the mechanism of the abnormalities of ameloblasts in mutant mice, we examined the expression of regulatory factors and tooth marker proteins (Figs. 4 and 5). It was shown that the homeobox-containing transcription factor Msx2 was expressed in undifferentiated ameloblasts but was down-regulated in secretory stage ameloblasts (Maas and Bei, 1997). P3 Ambn+/− ameloblasts expressed the Msx2 protein but its expression was diminished in P7 ameloblasts (Fig. 4). In mutant Amb−/− mice, Msx2 was expressed at P3 ameloblasts, similar to P3 Ambn+/− tooth. However, Msx2 was still expressed in a multiple cell layer of ameloblasts of P7 mutant tooth in contrast to P7 control tooth. p27, a Cdk inhibitor, was strongly expressed in P7 ameloblasts compared with P3 ameloblasts in Ambn+/− tooth (Bloch-Zupan et al., 1998), whereas its expression remained weak in P7 ameloblasts of mutant tooth. p75, a member of the TNF receptor family, was expressed in P3 Ambn+/− ameloblasts, and its expression was diminished at P7 (Mitsiadis et al., 1993). In contrast, p75 was expressed strongly in ameloblasts in P7 mutant tooth. Similar expression patterns of these proteins were observed in incisors containing all differentiation stages of the dental epithelium (unpublished data). Immunostaining of p27 was positive in immediate-early Ambn−/− ameloblasts, but it was reduced in the multicell layer of early secretory ameloblasts (unpublished data). This suggested that the proliferation of ameloblasts stopped at the immediate-early secretory stage but resumed from the early secretory stage. These results suggest that in mutant tooth, Ambn−/− ameloblasts regain certain early phenotypes of undifferentiated dental epithelium, when cells detach from the matrix and form a multicell layer.

Bottom Line: Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin.We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation.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.

View Article: PubMed Central - PubMed

Affiliation: Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.

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- 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.

Show MeSH
Related in: MedlinePlus