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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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Histology of molars and incisors and characterization of multilayered cells. (A) Hematoxylin-eosin staining of top first molars of E18, P1, P3, and P7 heterozygous (top) and homozygous (bottom) mice. Loss of cell polarity and detachment from the matrix were observed in P3. P7 molar ameloblast cells accumulate and fail to form columnar shaped single cell layers. (B) Incisors in 6-wk-old heterozygous (1) and homozygous (2) mice. High magnifications of the presecretory and secretory stages (3) and the early maturation stage (4) of mutant incisors. Ambn−/− ameloblasts form multiple layers containing abnormal calcified structures (arrows). Connective tissue (CT) was migrated into the detached space between ameloblasts and the matrix surface. Am, ameloblasts; D, dentin: EO, enamel organ; Od, odontoblasts; PS, presecretory stage; PD, predentin; P, pulp; E, enamel layer; arrows, calcified structures, dE; defective enamel. (C) Immunostaining of P7 normal (top) and mutant molars (bottom) with anti-amelogenin, enamelin, and tuftelin antibodies and Cy-3-conjugated secondary antibody. DAPI staining was used for nuclear localization. Dashed lines show the border between ameloblasts and the stratum intermedium interface (top) and margin of multilayered cells (bottom). Arrows indicate abnormal matrix accumulating enamel matrix proteins. (D) PCNA immunostaining of ameloblasts (right) and nuclear staining with Hoechst dye (left). am, ameloblast; si, stratum intermedium; en, enamel; sr, stellate reticulum. Bars, 25 μm.
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fig3: Histology of molars and incisors and characterization of multilayered cells. (A) Hematoxylin-eosin staining of top first molars of E18, P1, P3, and P7 heterozygous (top) and homozygous (bottom) mice. Loss of cell polarity and detachment from the matrix were observed in P3. P7 molar ameloblast cells accumulate and fail to form columnar shaped single cell layers. (B) Incisors in 6-wk-old heterozygous (1) and homozygous (2) mice. High magnifications of the presecretory and secretory stages (3) and the early maturation stage (4) of mutant incisors. Ambn−/− ameloblasts form multiple layers containing abnormal calcified structures (arrows). Connective tissue (CT) was migrated into the detached space between ameloblasts and the matrix surface. Am, ameloblasts; D, dentin: EO, enamel organ; Od, odontoblasts; PS, presecretory stage; PD, predentin; P, pulp; E, enamel layer; arrows, calcified structures, dE; defective enamel. (C) Immunostaining of P7 normal (top) and mutant molars (bottom) with anti-amelogenin, enamelin, and tuftelin antibodies and Cy-3-conjugated secondary antibody. DAPI staining was used for nuclear localization. Dashed lines show the border between ameloblasts and the stratum intermedium interface (top) and margin of multilayered cells (bottom). Arrows indicate abnormal matrix accumulating enamel matrix proteins. (D) PCNA immunostaining of ameloblasts (right) and nuclear staining with Hoechst dye (left). am, ameloblast; si, stratum intermedium; en, enamel; sr, stellate reticulum. Bars, 25 μm.

Mentions: In early molar development (E18), there were no differences in tooth size and shape between normal and Ambn−/− mice (Fig. 3 A). In P1 molars, dentin formation had begun and dental epithelium had started to elongate with the apical nuclear localization in both control and Ambn−/− mice. Thus, cellular organization of ameloblasts and odontoblasts was indistinguishable between normal and Ambn−/− mice at the presecretory stage. However, at P3, ameloblasts of Ambn−/− mice started to detach from the matrix layer and lose cell polarity seen as the centralized nuclear localization, whereas normal ameloblasts were polarized, elongated, and formed an enamel matrix (Fig. 3 A). At P7, Ambn−/− ameloblasts completely lost their polarity (short and round shape) and accumulated to form a multilayered structure, in contrast to the single layer of Ambn+/− ameloblasts. Similar to molars, cellular organization of presecretory stage ameloblasts of Ambn−/− incisors was normal (Fig. 3 B). At the early secretory stage, the mutant incisors have a zone where ameloblasts detach from the matrix and remain as a single cell layer. In the advanced stage, these cells lose polarity and form a multicell layer. In addition, connective tissues were formed underneath the detached ameloblast layer, which contained irregular calcified structures (Fig. 3 B, arrows). This calcified structure was confirmed by the presence of phosphocalcium in the energy dispersive analysis (unpublished data).


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)

Histology of molars and incisors and characterization of multilayered cells. (A) Hematoxylin-eosin staining of top first molars of E18, P1, P3, and P7 heterozygous (top) and homozygous (bottom) mice. Loss of cell polarity and detachment from the matrix were observed in P3. P7 molar ameloblast cells accumulate and fail to form columnar shaped single cell layers. (B) Incisors in 6-wk-old heterozygous (1) and homozygous (2) mice. High magnifications of the presecretory and secretory stages (3) and the early maturation stage (4) of mutant incisors. Ambn−/− ameloblasts form multiple layers containing abnormal calcified structures (arrows). Connective tissue (CT) was migrated into the detached space between ameloblasts and the matrix surface. Am, ameloblasts; D, dentin: EO, enamel organ; Od, odontoblasts; PS, presecretory stage; PD, predentin; P, pulp; E, enamel layer; arrows, calcified structures, dE; defective enamel. (C) Immunostaining of P7 normal (top) and mutant molars (bottom) with anti-amelogenin, enamelin, and tuftelin antibodies and Cy-3-conjugated secondary antibody. DAPI staining was used for nuclear localization. Dashed lines show the border between ameloblasts and the stratum intermedium interface (top) and margin of multilayered cells (bottom). Arrows indicate abnormal matrix accumulating enamel matrix proteins. (D) PCNA immunostaining of ameloblasts (right) and nuclear staining with Hoechst dye (left). am, ameloblast; si, stratum intermedium; en, enamel; sr, stellate reticulum. Bars, 25 μm.
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Related In: Results  -  Collection

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fig3: Histology of molars and incisors and characterization of multilayered cells. (A) Hematoxylin-eosin staining of top first molars of E18, P1, P3, and P7 heterozygous (top) and homozygous (bottom) mice. Loss of cell polarity and detachment from the matrix were observed in P3. P7 molar ameloblast cells accumulate and fail to form columnar shaped single cell layers. (B) Incisors in 6-wk-old heterozygous (1) and homozygous (2) mice. High magnifications of the presecretory and secretory stages (3) and the early maturation stage (4) of mutant incisors. Ambn−/− ameloblasts form multiple layers containing abnormal calcified structures (arrows). Connective tissue (CT) was migrated into the detached space between ameloblasts and the matrix surface. Am, ameloblasts; D, dentin: EO, enamel organ; Od, odontoblasts; PS, presecretory stage; PD, predentin; P, pulp; E, enamel layer; arrows, calcified structures, dE; defective enamel. (C) Immunostaining of P7 normal (top) and mutant molars (bottom) with anti-amelogenin, enamelin, and tuftelin antibodies and Cy-3-conjugated secondary antibody. DAPI staining was used for nuclear localization. Dashed lines show the border between ameloblasts and the stratum intermedium interface (top) and margin of multilayered cells (bottom). Arrows indicate abnormal matrix accumulating enamel matrix proteins. (D) PCNA immunostaining of ameloblasts (right) and nuclear staining with Hoechst dye (left). am, ameloblast; si, stratum intermedium; en, enamel; sr, stellate reticulum. Bars, 25 μm.
Mentions: In early molar development (E18), there were no differences in tooth size and shape between normal and Ambn−/− mice (Fig. 3 A). In P1 molars, dentin formation had begun and dental epithelium had started to elongate with the apical nuclear localization in both control and Ambn−/− mice. Thus, cellular organization of ameloblasts and odontoblasts was indistinguishable between normal and Ambn−/− mice at the presecretory stage. However, at P3, ameloblasts of Ambn−/− mice started to detach from the matrix layer and lose cell polarity seen as the centralized nuclear localization, whereas normal ameloblasts were polarized, elongated, and formed an enamel matrix (Fig. 3 A). At P7, Ambn−/− ameloblasts completely lost their polarity (short and round shape) and accumulated to form a multilayered structure, in contrast to the single layer of Ambn+/− ameloblasts. Similar to molars, cellular organization of presecretory stage ameloblasts of Ambn−/− incisors was normal (Fig. 3 B). At the early secretory stage, the mutant incisors have a zone where ameloblasts detach from the matrix and remain as a single cell layer. In the advanced stage, these cells lose polarity and form a multicell layer. In addition, connective tissues were formed underneath the detached ameloblast layer, which contained irregular calcified structures (Fig. 3 B, arrows). This calcified structure was confirmed by the presence of phosphocalcium in the energy dispersive analysis (unpublished data).

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