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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.

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Immunostaining of basement membrane and integrin in incisors. 6-wk-old mouse maxillas were fixed and decalcified. Paraffin sections of incisors of heterozygous and mutant mice were immunostained with antibodies to amelogenin, collagen IV, laminin 1, integrin α6, and laminin γ2 and visualized with Cy-3-conjugated secondary antibody. Polyclonal antibodies to laminin 1 react with α1, β1, and γ1. Laminin α1 is not present and the tooth basement membrane contains laminin 10 (α5, β1, and γ1). am, ameloblast; si, stratum intermedium; od, odontoblast; en, enamel; de, dentin.
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fig6: Immunostaining of basement membrane and integrin in incisors. 6-wk-old mouse maxillas were fixed and decalcified. Paraffin sections of incisors of heterozygous and mutant mice were immunostained with antibodies to amelogenin, collagen IV, laminin 1, integrin α6, and laminin γ2 and visualized with Cy-3-conjugated secondary antibody. Polyclonal antibodies to laminin 1 react with α1, β1, and γ1. Laminin α1 is not present and the tooth basement membrane contains laminin 10 (α5, β1, and γ1). am, ameloblast; si, stratum intermedium; od, odontoblast; en, enamel; de, dentin.

Mentions: The basement membrane provides a scaffolding for epithelium and signaling for cellular differentiation in many tissues through interactions of specific cellular receptors (Yurchenco and O'Rear, 1994; Timpl, 1996). Because secretory stage ameloblasts of Ambn−/− mice showed loss of cell polarity and abnormal proliferation with detachment from the matrix, we examined the basement membrane by immunostaining normal and Ambn−/− incisors (Fig. 6). In normal incisors, localization patterns of the basement membrane (stained for collagen IV and laminin β1/γ1 [subunits of laminin 10/11, a major laminin in early tooth development]) and enamel matrix (stained for ameloblastin) were reciprocal (Fig. 6). The basement membrane was present at the basal lamina underneath presecretory stage ameloblasts (preameloblasts), however, at the secretory stage they disappeared and the enamel matrix emerged with some overlapping in the intermediate stage (enamel layer indicated by dotted lines). Expression patterns of integrin α6, a receptor of laminin, are similar to that of the basement membrane: it was localized at the basal layer of preameloblasts, but disappeared when preameloblasts differentiated into ameloblasts. In mutant incisors, the expression patterns of the basement membrane and integrin α6 were similar to normal incisors. It was reported that laminin 5, epithelial laminin consisting of α3β3γ2, was synthesized by secretory stage ameloblasts (Salmivirta et al., 1997; Ryan et al., 1999). Weak expression of the laminin γ2 chain was observed at the early secretory stage, and its strong expression started at the late secretory stage and continued through the maturation stage, indicating that its expression is delayed compared with ameloblastin (Fig. 6). Significant staining of the laminin γ2 chain was observed in the basal cytoplasm part of late secretory ameloblasts. This localization pattern is different from that of laminin β1/γ1 immunostaining where most of the staining was found in the basal lamina. In the mutant, laminin γ2 was synthesized and deposited in the matrix surrounding abnormally accumulated ameloblasts. There is no difference in basement membrane formation between normal and mutant teeth at the presecretory stage. However, in a more advanced secretory stage, where ameloblastin is synthesized, abnormalities are obvious and progressive. Thus, ameloblastin is a candidate matrix protein for supporting secretory stage ameloblasts.


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)

Immunostaining of basement membrane and integrin in incisors. 6-wk-old mouse maxillas were fixed and decalcified. Paraffin sections of incisors of heterozygous and mutant mice were immunostained with antibodies to amelogenin, collagen IV, laminin 1, integrin α6, and laminin γ2 and visualized with Cy-3-conjugated secondary antibody. Polyclonal antibodies to laminin 1 react with α1, β1, and γ1. Laminin α1 is not present and the tooth basement membrane contains laminin 10 (α5, β1, and γ1). am, ameloblast; si, stratum intermedium; od, odontoblast; en, enamel; de, dentin.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2172447&req=5

fig6: Immunostaining of basement membrane and integrin in incisors. 6-wk-old mouse maxillas were fixed and decalcified. Paraffin sections of incisors of heterozygous and mutant mice were immunostained with antibodies to amelogenin, collagen IV, laminin 1, integrin α6, and laminin γ2 and visualized with Cy-3-conjugated secondary antibody. Polyclonal antibodies to laminin 1 react with α1, β1, and γ1. Laminin α1 is not present and the tooth basement membrane contains laminin 10 (α5, β1, and γ1). am, ameloblast; si, stratum intermedium; od, odontoblast; en, enamel; de, dentin.
Mentions: The basement membrane provides a scaffolding for epithelium and signaling for cellular differentiation in many tissues through interactions of specific cellular receptors (Yurchenco and O'Rear, 1994; Timpl, 1996). Because secretory stage ameloblasts of Ambn−/− mice showed loss of cell polarity and abnormal proliferation with detachment from the matrix, we examined the basement membrane by immunostaining normal and Ambn−/− incisors (Fig. 6). In normal incisors, localization patterns of the basement membrane (stained for collagen IV and laminin β1/γ1 [subunits of laminin 10/11, a major laminin in early tooth development]) and enamel matrix (stained for ameloblastin) were reciprocal (Fig. 6). The basement membrane was present at the basal lamina underneath presecretory stage ameloblasts (preameloblasts), however, at the secretory stage they disappeared and the enamel matrix emerged with some overlapping in the intermediate stage (enamel layer indicated by dotted lines). Expression patterns of integrin α6, a receptor of laminin, are similar to that of the basement membrane: it was localized at the basal layer of preameloblasts, but disappeared when preameloblasts differentiated into ameloblasts. In mutant incisors, the expression patterns of the basement membrane and integrin α6 were similar to normal incisors. It was reported that laminin 5, epithelial laminin consisting of α3β3γ2, was synthesized by secretory stage ameloblasts (Salmivirta et al., 1997; Ryan et al., 1999). Weak expression of the laminin γ2 chain was observed at the early secretory stage, and its strong expression started at the late secretory stage and continued through the maturation stage, indicating that its expression is delayed compared with ameloblastin (Fig. 6). Significant staining of the laminin γ2 chain was observed in the basal cytoplasm part of late secretory ameloblasts. This localization pattern is different from that of laminin β1/γ1 immunostaining where most of the staining was found in the basal lamina. In the mutant, laminin γ2 was synthesized and deposited in the matrix surrounding abnormally accumulated ameloblasts. There is no difference in basement membrane formation between normal and mutant teeth at the presecretory stage. However, in a more advanced secretory stage, where ameloblastin is synthesized, abnormalities are obvious and progressive. Thus, ameloblastin is a candidate matrix protein for supporting secretory stage ameloblasts.

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