Eplthelial-Mesenchymal Signaling during Tooth Development

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Abstract
Classic studies on experimental embryology have shown that organ development in an embryo is largely regulated by so called inductive tissue interactions which mostly take place between epithelial and mesenchymal tissues. Also in the developing tooth, both morphogenesis and cell differentiation are governed by such interactions. Characteristic features of epithelial-mesenchymal interactions are that they are sequential and reciprocal, i.e. “induction” appears to consist of a chain of signaling events between the tissues. During the last decade, the expression patterns of numerous molecules have been studied in developing organs by in situ hybridization and immunohistology. Many of them have been associated with epithelial-mesenchymal interactions, and it is apparent that same molecules participate in regulation of morphogenesis in a number of different organs. Transcription factors such as Msx-1, Msx-2 and Egr-1, growth factors, including TGFB's, BMPs, and FGFs, and structural proteins such as syndecan and tenascin are expressed in transient, time and space-specific patterns in many organ rudiments, including the tooth. We have shown by tissue recombination studies that the expression of certain molecules is indeed regulated by epithelial-mesenchymal interactions in the early tooth germ. In particular, during the early stages of morphogenesis, when the dental epithelium induces the condensation of mesenchymal cells around the epithelial bud, the expression of many genes is upregulated in the condensed mesenchyme. Previous experimental tissue recombination studies have indicated that at the same time the capacity to instruct tooth morphogenesis shifts from the dental epithelium to the dental mesenchyme. During mesoderm formation in Xenopus embryo, growth factors belonging to the TGFβ and FGF families act as inductive signals between tissues. There is increasing evidence that growth factors transmit induction also during epithelial-mesenchymal interactions in developing organs. Evidence from in situ hybridization analyses of growth factor expression as well as recent experimental studies, in which local effects of growth factors have been analysed in dental tissues, suggest that BMP-2 and BMP-4 may mediate tissue interactions. Specifically, epithelial BMPs may induce the determination of the dental mesenchyme by regulating the expression of homeobox-containing genes Msx-1 and Msx-2. These “master genes” may control subsequent expression of other, later signaling molecules and of structural molecules regulating morphogenesis of the dental tissues.