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Nfic regulates tooth root patterning and growth.

Kim TH, Bae CH, Yang S, Park JC, Cho ES - Anat Cell Biol (2015)

Bottom Line: In contrast, cytokeratin 14 and Smo were localized in the cells of the furcation region of mutant molars.These results indicate that Nfic regulates cell proliferation in the dental mesenchyme and affects the fate of HERS cells in a site-specific manner.From the results, it is suggested that Nfic is required for root patterning and growth during root morphogenesis.

View Article: PubMed Central - PubMed

Affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju, Korea.

ABSTRACT
Molecular interactions between epithelium and mesenchyme are important for root formation. Nuclear factor I-C (Nfic) has been identified as a key regulator of root formation. However, the mechanisms of root formation and their interactions between Hertwig's epithelial root sheath (HERS) and mesenchyme remain unclear. In this study, we investigated the role of Nfic in root patterning and growth during molar root development. The molars of Nfic knockout mice exhibited an enlarged pulp chamber and apical displacement of the pulpal floor, characteristic features of taurodontism, due to delayed furcation formation. In developing molar roots of mutant mice at P14, BrdU positive cells decreased in the apical mesenchyme of the elongation region whereas those cells increased in the dental papilla of the furcation region. Whereas cytokeratin 14 and laminin were localized in HERS cells of mutant molars, Smoothened (Smo) and Gli1 were downregulated in preodontoblasts. In contrast, cytokeratin 14 and Smo were localized in the cells of the furcation region of mutant molars. These results indicate that Nfic regulates cell proliferation in the dental mesenchyme and affects the fate of HERS cells in a site-specific manner. From the results, it is suggested that Nfic is required for root patterning and growth during root morphogenesis.

No MeSH data available.


Related in: MedlinePlus

Localization of nuclear factor I-C (Nfic), Phex, cytokeratin 14 (CK14), and Smo in the furcation region of developing mandibular first molar of Nfic knockout mice at P14. (A, B) In wild type (WT) mice, Nfic was localized in odontoblasts and cells in the pulp and periodontium, whereas no immunoreactivity was observed in mutant (MT) mice. (C, D) Phex was localized in odontoblasts of both WT and MT mice. (E, F) CK14 was localized in the epithelial rests below the inter-radicular dentin dentin at the furcation region in both WT and MT mice. (G, H) Smo was localized in the odontoblasts and cells in the periodontium in WT mice. In MT mice, localization of Smo was found around Hertwig's epithelial root sheath (HERS). The black arrows indicate HERS. Ab, alveolar bone; P, pulp; Ird, inter-radicular dentin dentin at the furcation region; Od, odontoblasts. Scale bar=80 µm.
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Figure 4: Localization of nuclear factor I-C (Nfic), Phex, cytokeratin 14 (CK14), and Smo in the furcation region of developing mandibular first molar of Nfic knockout mice at P14. (A, B) In wild type (WT) mice, Nfic was localized in odontoblasts and cells in the pulp and periodontium, whereas no immunoreactivity was observed in mutant (MT) mice. (C, D) Phex was localized in odontoblasts of both WT and MT mice. (E, F) CK14 was localized in the epithelial rests below the inter-radicular dentin dentin at the furcation region in both WT and MT mice. (G, H) Smo was localized in the odontoblasts and cells in the periodontium in WT mice. In MT mice, localization of Smo was found around Hertwig's epithelial root sheath (HERS). The black arrows indicate HERS. Ab, alveolar bone; P, pulp; Ird, inter-radicular dentin dentin at the furcation region; Od, odontoblasts. Scale bar=80 µm.

Mentions: We performed immunohistochemical stains to assess molecular changes in the developing molar roots following disruption of Nfic. Comparable molecular changes in the developing molar roots following Nfic disruption were observed at P10 (Fig. 3). In the elongation region, HERS cells of both WT and MT mice were marked by CK14 (Fig. 3A, E). HERS was thin and short in WT mice, but was longer in MT mice. Laminin, a component of the basement membrane, was localized around HERS both of WT and MT mice (Fig. 3B, F). Localization of Smo, a signal transducer of Shh signaling [6], was overlapped in the membrane of HERS cells in WT mice (Fig. 3C). However, Smo was downregulated in the HERS cells of MT mice. Weak Smo immunoreactivities were observed in the region between the inner layer of HERS and adjacent pulp cells (Fig. 3G). Gli1, a transcription factor activated by Shh [14], was widely localized in odontoblasts, pulp cells, and HERS cells of WT mice (Fig. 3D). In MT mice, Gli1 was also widely localized in the cells of HERS and pulp core except preodontoblasts, dental papilla cells close to the inner layer of HERS (Fig. 3H). In the furcation region of WT mice at P14, Nfic was localized in the odontoblasts and cells in the pulp and periodontium, whereas no immunoreactivity was observed in MT mice (Fig. 4A, B). Phex, a marker for mature odontoblasts, was localized in the odontoblasts of both WT and MT mice (Fig. 4C, D). Both in WT and MT mice, the epithelial rests below the inter-radicular dentin dentin at the furcation region were marked by CK14 (Fig. 4E, F). In WT mice, Smo was localized in the odontoblasts and cells in the periodontium (Fig. 4G). Localization of Smo was found around the epithelial cells in MT mice (Fig. 4H).


Nfic regulates tooth root patterning and growth.

Kim TH, Bae CH, Yang S, Park JC, Cho ES - Anat Cell Biol (2015)

Localization of nuclear factor I-C (Nfic), Phex, cytokeratin 14 (CK14), and Smo in the furcation region of developing mandibular first molar of Nfic knockout mice at P14. (A, B) In wild type (WT) mice, Nfic was localized in odontoblasts and cells in the pulp and periodontium, whereas no immunoreactivity was observed in mutant (MT) mice. (C, D) Phex was localized in odontoblasts of both WT and MT mice. (E, F) CK14 was localized in the epithelial rests below the inter-radicular dentin dentin at the furcation region in both WT and MT mice. (G, H) Smo was localized in the odontoblasts and cells in the periodontium in WT mice. In MT mice, localization of Smo was found around Hertwig's epithelial root sheath (HERS). The black arrows indicate HERS. Ab, alveolar bone; P, pulp; Ird, inter-radicular dentin dentin at the furcation region; Od, odontoblasts. Scale bar=80 µm.
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Related In: Results  -  Collection

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Show All Figures
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Figure 4: Localization of nuclear factor I-C (Nfic), Phex, cytokeratin 14 (CK14), and Smo in the furcation region of developing mandibular first molar of Nfic knockout mice at P14. (A, B) In wild type (WT) mice, Nfic was localized in odontoblasts and cells in the pulp and periodontium, whereas no immunoreactivity was observed in mutant (MT) mice. (C, D) Phex was localized in odontoblasts of both WT and MT mice. (E, F) CK14 was localized in the epithelial rests below the inter-radicular dentin dentin at the furcation region in both WT and MT mice. (G, H) Smo was localized in the odontoblasts and cells in the periodontium in WT mice. In MT mice, localization of Smo was found around Hertwig's epithelial root sheath (HERS). The black arrows indicate HERS. Ab, alveolar bone; P, pulp; Ird, inter-radicular dentin dentin at the furcation region; Od, odontoblasts. Scale bar=80 µm.
Mentions: We performed immunohistochemical stains to assess molecular changes in the developing molar roots following disruption of Nfic. Comparable molecular changes in the developing molar roots following Nfic disruption were observed at P10 (Fig. 3). In the elongation region, HERS cells of both WT and MT mice were marked by CK14 (Fig. 3A, E). HERS was thin and short in WT mice, but was longer in MT mice. Laminin, a component of the basement membrane, was localized around HERS both of WT and MT mice (Fig. 3B, F). Localization of Smo, a signal transducer of Shh signaling [6], was overlapped in the membrane of HERS cells in WT mice (Fig. 3C). However, Smo was downregulated in the HERS cells of MT mice. Weak Smo immunoreactivities were observed in the region between the inner layer of HERS and adjacent pulp cells (Fig. 3G). Gli1, a transcription factor activated by Shh [14], was widely localized in odontoblasts, pulp cells, and HERS cells of WT mice (Fig. 3D). In MT mice, Gli1 was also widely localized in the cells of HERS and pulp core except preodontoblasts, dental papilla cells close to the inner layer of HERS (Fig. 3H). In the furcation region of WT mice at P14, Nfic was localized in the odontoblasts and cells in the pulp and periodontium, whereas no immunoreactivity was observed in MT mice (Fig. 4A, B). Phex, a marker for mature odontoblasts, was localized in the odontoblasts of both WT and MT mice (Fig. 4C, D). Both in WT and MT mice, the epithelial rests below the inter-radicular dentin dentin at the furcation region were marked by CK14 (Fig. 4E, F). In WT mice, Smo was localized in the odontoblasts and cells in the periodontium (Fig. 4G). Localization of Smo was found around the epithelial cells in MT mice (Fig. 4H).

Bottom Line: In contrast, cytokeratin 14 and Smo were localized in the cells of the furcation region of mutant molars.These results indicate that Nfic regulates cell proliferation in the dental mesenchyme and affects the fate of HERS cells in a site-specific manner.From the results, it is suggested that Nfic is required for root patterning and growth during root morphogenesis.

View Article: PubMed Central - PubMed

Affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju, Korea.

ABSTRACT
Molecular interactions between epithelium and mesenchyme are important for root formation. Nuclear factor I-C (Nfic) has been identified as a key regulator of root formation. However, the mechanisms of root formation and their interactions between Hertwig's epithelial root sheath (HERS) and mesenchyme remain unclear. In this study, we investigated the role of Nfic in root patterning and growth during molar root development. The molars of Nfic knockout mice exhibited an enlarged pulp chamber and apical displacement of the pulpal floor, characteristic features of taurodontism, due to delayed furcation formation. In developing molar roots of mutant mice at P14, BrdU positive cells decreased in the apical mesenchyme of the elongation region whereas those cells increased in the dental papilla of the furcation region. Whereas cytokeratin 14 and laminin were localized in HERS cells of mutant molars, Smoothened (Smo) and Gli1 were downregulated in preodontoblasts. In contrast, cytokeratin 14 and Smo were localized in the cells of the furcation region of mutant molars. These results indicate that Nfic regulates cell proliferation in the dental mesenchyme and affects the fate of HERS cells in a site-specific manner. From the results, it is suggested that Nfic is required for root patterning and growth during root morphogenesis.

No MeSH data available.


Related in: MedlinePlus