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Localization of putative stem cells in dental epithelium and their association with Notch and FGF signaling.

Harada H, Kettunen P, Jung HS, Mustonen T, Wang YA, Thesleff I - J. Cell Biol. (1999)

Bottom Line: It is known from tissue recombination studies that in the mouse incisor the mesenchyme regulates the continuous growth of epithelium.When FGF-10 protein was applied with beads on the cultured cervical loop epithelium it stimulated cell proliferation as well as expression of lunatic fringe.We present a model in which FGF signaling from the mesenchyme regulates the Notch pathway in dental epithelial stem cells via stimulation of lunatic fringe expression and, thereby, has a central role in coupling the mitogenesis and fate decision of stem cells.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biology Programme, Institute of Biotechnology, Viikki Biocenter, University of Helsinki, 00014 Helsinki, Finland.

ABSTRACT
The continuously growing mouse incisor is an excellent model to analyze the mechanisms for stem cell lineage. We designed an organ culture method for the apical end of the incisor and analyzed the epithelial cell lineage by 5-bromo-2'-deoxyuridine and DiI labeling. Our results indicate that stem cells reside in the cervical loop epithelium consisting of a central core of stellate reticulum cells surrounded by a layer of basal epithelial cells, and that they give rise to transit-amplifying progeny differentiating into enamel forming ameloblasts. We identified slowly dividing cells among the Notch1-expressing stellate reticulum cells in specific locations near the basal epithelial cells expressing lunatic fringe, a secretory molecule modulating Notch signaling. It is known from tissue recombination studies that in the mouse incisor the mesenchyme regulates the continuous growth of epithelium. Expression of Fgf-3 and Fgf-10 were restricted to the mesenchyme underlying the basal epithelial cells and the transit-amplifying cells expressing their receptors Fgfr1b and Fgfr2b. When FGF-10 protein was applied with beads on the cultured cervical loop epithelium it stimulated cell proliferation as well as expression of lunatic fringe. We present a model in which FGF signaling from the mesenchyme regulates the Notch pathway in dental epithelial stem cells via stimulation of lunatic fringe expression and, thereby, has a central role in coupling the mitogenesis and fate decision of stem cells.

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Localization of Fgf-3 and Fgf-10 and the receptors Fgfr1b and Fgfr2b (Kgfr) mRNA in the mandibular incisor of 2-d-old mice. (a and c) Fgf-10 is intensely expressed in the dental mesenchyme adjacent to cervical loop and inner enamel epithelium. (b and d) Fgfr1b is expressed throughout cervical loop epithelium with high intensity at the border between basal epithelial cells and stellate reticulum. (e) Fgf-3 is expressed in dental mesenchyme under the inner enamel epithelium in a more restricted area than Fgf-10. (f) Fgfr2b (Kgfr) is expressed in the cervical loop in similar locations as Fgfr1b. c and d show higher magnification of the cervical loop in a and b, respectively. Bars: (a, b, e, and f) 1 mm; (c and d) 200 μm.
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Figure 7: Localization of Fgf-3 and Fgf-10 and the receptors Fgfr1b and Fgfr2b (Kgfr) mRNA in the mandibular incisor of 2-d-old mice. (a and c) Fgf-10 is intensely expressed in the dental mesenchyme adjacent to cervical loop and inner enamel epithelium. (b and d) Fgfr1b is expressed throughout cervical loop epithelium with high intensity at the border between basal epithelial cells and stellate reticulum. (e) Fgf-3 is expressed in dental mesenchyme under the inner enamel epithelium in a more restricted area than Fgf-10. (f) Fgfr2b (Kgfr) is expressed in the cervical loop in similar locations as Fgfr1b. c and d show higher magnification of the cervical loop in a and b, respectively. Bars: (a, b, e, and f) 1 mm; (c and d) 200 μm.

Mentions: Earlier tissue recombination experiments have shown that dental mesenchyme controls the morphogenesis of dental epithelium (Kollar and Baird 1969) including the continuous growth of the incisor epithelium (Jernvall, J., personal communication), and our recent studies on early tooth morphogenesis have implicated FGFs-3 and -10 as mesenchymal signals regulating the early morphogenesis of dental epithelium (Kettunen, P., N. Itoh, and I. Thesleff, manuscript submitted for publication). Hence, we analyzed the patterns of the expression of these signals as well as their receptors by in situ hybridization in the 2-d-old mouse incisors. Both Fgfs were intensely expressed in a restricted area of the dental mesenchyme in the apical end of the tooth. Fgf-10 expressing cells surrounded the whole cervical loop epithelium and extended to the zone underlying inner enamel epithelium (Fig. 7, a and c). Fgf-3 showed a more restricted pattern of expression. It overlapped with Fgf-10 in the mesenchyme under the inner enamel epithelium, but was not expressed in the mesenchyme surrounding the cervical loop (Fig. 7 e). Fgfr1b was intensely expressed in the cervical loop epithelium including the basal epithelial cells and stratum intermedium, but was less intense in the stellate reticulum cells (Fig. 7b and Fig. d), and Fgfr2b (Kgfr) showed a similar pattern in the cervical loop (Fig. 7 f). Hence, the patterns of the expression of Fgf-3 and Fgf-10 and their receptors were in line with the suggestion that these FGFs may be mesenchymal signals regulating the development of cervical loop epithelium.


Localization of putative stem cells in dental epithelium and their association with Notch and FGF signaling.

Harada H, Kettunen P, Jung HS, Mustonen T, Wang YA, Thesleff I - J. Cell Biol. (1999)

Localization of Fgf-3 and Fgf-10 and the receptors Fgfr1b and Fgfr2b (Kgfr) mRNA in the mandibular incisor of 2-d-old mice. (a and c) Fgf-10 is intensely expressed in the dental mesenchyme adjacent to cervical loop and inner enamel epithelium. (b and d) Fgfr1b is expressed throughout cervical loop epithelium with high intensity at the border between basal epithelial cells and stellate reticulum. (e) Fgf-3 is expressed in dental mesenchyme under the inner enamel epithelium in a more restricted area than Fgf-10. (f) Fgfr2b (Kgfr) is expressed in the cervical loop in similar locations as Fgfr1b. c and d show higher magnification of the cervical loop in a and b, respectively. Bars: (a, b, e, and f) 1 mm; (c and d) 200 μm.
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Figure 7: Localization of Fgf-3 and Fgf-10 and the receptors Fgfr1b and Fgfr2b (Kgfr) mRNA in the mandibular incisor of 2-d-old mice. (a and c) Fgf-10 is intensely expressed in the dental mesenchyme adjacent to cervical loop and inner enamel epithelium. (b and d) Fgfr1b is expressed throughout cervical loop epithelium with high intensity at the border between basal epithelial cells and stellate reticulum. (e) Fgf-3 is expressed in dental mesenchyme under the inner enamel epithelium in a more restricted area than Fgf-10. (f) Fgfr2b (Kgfr) is expressed in the cervical loop in similar locations as Fgfr1b. c and d show higher magnification of the cervical loop in a and b, respectively. Bars: (a, b, e, and f) 1 mm; (c and d) 200 μm.
Mentions: Earlier tissue recombination experiments have shown that dental mesenchyme controls the morphogenesis of dental epithelium (Kollar and Baird 1969) including the continuous growth of the incisor epithelium (Jernvall, J., personal communication), and our recent studies on early tooth morphogenesis have implicated FGFs-3 and -10 as mesenchymal signals regulating the early morphogenesis of dental epithelium (Kettunen, P., N. Itoh, and I. Thesleff, manuscript submitted for publication). Hence, we analyzed the patterns of the expression of these signals as well as their receptors by in situ hybridization in the 2-d-old mouse incisors. Both Fgfs were intensely expressed in a restricted area of the dental mesenchyme in the apical end of the tooth. Fgf-10 expressing cells surrounded the whole cervical loop epithelium and extended to the zone underlying inner enamel epithelium (Fig. 7, a and c). Fgf-3 showed a more restricted pattern of expression. It overlapped with Fgf-10 in the mesenchyme under the inner enamel epithelium, but was not expressed in the mesenchyme surrounding the cervical loop (Fig. 7 e). Fgfr1b was intensely expressed in the cervical loop epithelium including the basal epithelial cells and stratum intermedium, but was less intense in the stellate reticulum cells (Fig. 7b and Fig. d), and Fgfr2b (Kgfr) showed a similar pattern in the cervical loop (Fig. 7 f). Hence, the patterns of the expression of Fgf-3 and Fgf-10 and their receptors were in line with the suggestion that these FGFs may be mesenchymal signals regulating the development of cervical loop epithelium.

Bottom Line: It is known from tissue recombination studies that in the mouse incisor the mesenchyme regulates the continuous growth of epithelium.When FGF-10 protein was applied with beads on the cultured cervical loop epithelium it stimulated cell proliferation as well as expression of lunatic fringe.We present a model in which FGF signaling from the mesenchyme regulates the Notch pathway in dental epithelial stem cells via stimulation of lunatic fringe expression and, thereby, has a central role in coupling the mitogenesis and fate decision of stem cells.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biology Programme, Institute of Biotechnology, Viikki Biocenter, University of Helsinki, 00014 Helsinki, Finland.

ABSTRACT
The continuously growing mouse incisor is an excellent model to analyze the mechanisms for stem cell lineage. We designed an organ culture method for the apical end of the incisor and analyzed the epithelial cell lineage by 5-bromo-2'-deoxyuridine and DiI labeling. Our results indicate that stem cells reside in the cervical loop epithelium consisting of a central core of stellate reticulum cells surrounded by a layer of basal epithelial cells, and that they give rise to transit-amplifying progeny differentiating into enamel forming ameloblasts. We identified slowly dividing cells among the Notch1-expressing stellate reticulum cells in specific locations near the basal epithelial cells expressing lunatic fringe, a secretory molecule modulating Notch signaling. It is known from tissue recombination studies that in the mouse incisor the mesenchyme regulates the continuous growth of epithelium. Expression of Fgf-3 and Fgf-10 were restricted to the mesenchyme underlying the basal epithelial cells and the transit-amplifying cells expressing their receptors Fgfr1b and Fgfr2b. When FGF-10 protein was applied with beads on the cultured cervical loop epithelium it stimulated cell proliferation as well as expression of lunatic fringe. We present a model in which FGF signaling from the mesenchyme regulates the Notch pathway in dental epithelial stem cells via stimulation of lunatic fringe expression and, thereby, has a central role in coupling the mitogenesis and fate decision of stem cells.

Show MeSH