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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Ameloblasts / cytology*
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Ameloblasts / drug effects
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Ameloblasts / metabolism
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Animals
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Calcium-Binding Proteins
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Cell Lineage / drug effects
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Culture Techniques
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Fibroblast Growth Factor 10
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Fibroblast Growth Factor 3
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Fibroblast Growth Factors / metabolism
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Fibroblast Growth Factors / pharmacology*
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Gene Expression Regulation / drug effects
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Glycosyltransferases*
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Incisor / cytology*
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Incisor / drug effects
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Incisor / metabolism
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Intercellular Signaling Peptides and Proteins
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Jagged-1 Protein
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Membrane Proteins / genetics
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Membrane Proteins / physiology*
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Mesoderm / drug effects
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Mesoderm / metabolism
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Mice
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Mice, Inbred Strains
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Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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Receptors, Fibroblast Growth Factor / metabolism
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Receptors, Notch
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Regeneration
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Serrate-Jagged Proteins
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Signal Transduction / drug effects*
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Stem Cells / cytology*
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Stem Cells / drug effects
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Stem Cells / metabolism
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Xenopus Proteins*
Substances
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Calcium-Binding Proteins
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FGF3 protein, Xenopus
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Fgf10 protein, mouse
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Fgf3 protein, mouse
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Fibroblast Growth Factor 10
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Fibroblast Growth Factor 3
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Intercellular Signaling Peptides and Proteins
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Jagged-1 Protein
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Membrane Proteins
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Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Receptors, Fibroblast Growth Factor
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Receptors, Notch
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Serrate-Jagged Proteins
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Xenopus Proteins
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jag1 protein, Xenopus
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Fibroblast Growth Factors
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Glycosyltransferases
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Lfng protein, mouse