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PMID: 7615640 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression of Notch 1, 2 and 3 is regulated by epithelial-mesenchymal interactions and retinoic acid in the developing mouse tooth and associated with determination of ameloblast cell fate.

The Journal of cell biology ·Vol. 130 ·No. 2 ·1995-07-00 ·Pages 407-18

Mitsiadis TA, Lardelli M, Lendahl U, Thesleff I

Abstract

Notch 1, Notch 2, and Notch 3 are three highly conserved mammalian homologues of the Drosophila Notch gene, which encodes a transmembrane protein important for various cell fate decisions during development. Little is yet known about regulation of mammalian Notch gene expression, and this issue has been addressed in the developing rodent tooth during normal morphogenesis and after experimental manipulation. Notch 1, 2, and 3 genes show distinct cell-type specific expression patterns. Most notably, Notch expression is absent in epithelial cells in close contact with mesenchyme, which may be important for acquisition of the ameloblast fate. This reveals a previously unknown prepatterning of dental epithelium at early stages, and suggests that mesenchyme negatively regulates Notch expression in epithelium. This hypothesis has been tested in homo- and heterotypic explant experiments in vitro. The data show that Notch expression is downregulated in dental epithelial cells juxtaposed to mesenchyme, indicating that dental epithelium needs a mesenchyme-derived signal in order to maintain the downregulation of Notch. Finally, Notch expression in dental mesenchyme is upregulated in a region surrounding beads soaked in retinoic acid (50-100 micrograms/ml) but not in fibroblast growth factor-2 (100-250 micrograms/ml). The response to retinoic acid was seen in explants of 11-12-d old mouse embryos but not in older embryos. These data suggest that Notch genes may be involved in mediating some of the biological effects of retinoic acid during normal development and after teratogenic exposure.

MeSH Terms
Ameloblasts/cytology Animals Cell Differentiation Epithelium/physiology Fibroblast Growth Factors/pharmacology Gene Expression Regulation/drug effects In Situ Hybridization Membrane Proteins/analysis,genetics Mesoderm/physiology Mice Mice, Inbred Strains Odontoblasts/cytology Odontogenesis/genetics,physiology Proto-Oncogene Proteins/analysis,genetics RNA, Messenger/analysis,genetics Receptor, Notch1 Receptor, Notch2 Receptor, Notch4 Receptors, Cell Surface/analysis,genetics Receptors, Notch Transcription Factors Tretinoin/pharmacology
Chemicals
Membrane Proteins Notch1 protein, mouse Notch2 protein, mouse Proto-Oncogene Proteins RNA, Messenger Receptor, Notch1 Receptor, Notch2 Receptor, Notch4 Receptors, Cell Surface Receptors, Notch Transcription Factors Notch4 protein, mouse Tretinoin Fibroblast Growth Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Mitsiadis T A
Department of Pedodontics and Orthodontics, University of Helsinki, Finland.
Lardelli M
Lendahl U
Thesleff I
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.130.2.407
Published
1995-07-00
Pages
407-18
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2199945
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.130.2.407 PMC Full Text View journal details
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