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© The Rockefeller University Press, 0021-9525/1999//105 $5.00
The Journal of Cell Biology, Volume 147, Number 1, , 1999 105-120

Original Article

Localization of Putative Stem Cells in Dental Epithelium and Their Association with Notch and Fgf Signaling



Hidemitsu Haradaa, Päivi Kettunena, Han-Sung Junga, Tuija Mustonena, Y. Alan Wangb, and Irma Thesleffa

a Developmental Biology Programme, Institute of Biotechnology, Viikki Biocenter, University of Helsinki, 00014 Helsinki, Finland
b Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115
Developmental Biology Programme, Institute of Biotechnology, P.O. Box 56, FIN-00014, University of Helsinki, Finland.358-9-708-59560358-9-70859-401

thesleff{at}operoni.helsinki.fi

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.

Key Words: ameloblast • Notch • fringe • Fgf-10 • epithelial–mesenchymal interactions

© 1999 The Rockefeller University Press

1.used in this paper: BrdU, 5-bromo-2'-deoxyuridine; DiI, 1,1'-dioctadecyl-6,6-di(4-sulfophenyl)-3,3,3',3'-tetramethylindocarbocyanine; FGF, fibroblast growth factor

The present address of Hidemitsu Harada is Second Department of Oral Anatomy and Cell Biology, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu-shi, 803-8580, Japan.


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