Molecular mechanisms of cell and tissue interactions during early tooth development.

Background: Morphogenesis and cell differentiation during the development of all organs, including the tooth, are regulated by interactions between cells and tissues. The developing tooth is one of the organs in which the molecular mechanisms of such interactions are starting to be elucidated.

Results: Homotypic cell interactions take place between cells of the same developmental history, and they are a central mechanism in the formation of mesenchymal cell condensates during the bud stage of tooth development. Syndecan-1, a cell surface heparan sulfate proteoglycan, is transiently expressed in the dental mesenchyme and may regulate dental mesenchymal cell condensation. It binds tenascin, a matrix glycoprotein abundant in dental mesenchyme, suggesting involvement of cell-matrix interactions. Syndecan also binds growth factors, and its association with cell proliferation in the dental mesenchyme suggests roles in the regulation of cell number in the condensing cells. Inductive interactions between the epithelial and mesenchymal tissues regulate tooth development at all stages. In the early dental mesenchyme, the expression of several molecules, including syndecan and tenascin, are regulated by the epithelium. There is evidence that growth factors act as diffusible signals mediating these interactions. BMP-2 and BMP-4 (bone morphogenetic proteins), which belong to the TGF beta superfamily, are expressed in the early dental epithelium, and their effects on the dental mesenchyme mimic those of the epithelium. In particular, BMPs induce the expression of the homeobox-containing transcription factors Msx-1 and Msx-2 in the dental mesenchyme.

Conclusions: Based on current knowledge about the molecular changes accompanying tooth development and the results of experimental studies, we present a model for molecular regulation of early tooth development.