Growth factors as inductive signals regulating tooth morphogenesis

Teeth are typical examples of organs, the morphogenesis of which is regulated by interactions between epithelial and mesenchymal tissue components. The analysis of expression patterns of a number of growth factors, and the examination of their effects in vitro by local application on isolated dental tissues, has provided increasing evidence that growth factors act as inductive signals. Growth factors in the BMP- and FGF-families are expressed in dental epithelium during initiation of tooth development and their effects on the underlying mesenchyme mimic those of the epithelium. They upregulate the expression of many genes, including the homeobox-containing Msx-1 and Msx-2, and stimulate cell proliferation suggesting that they may act as epithelial signals transmitting epithelial-mesenchymal interactions. During subsequent morphogenesis, when the characteristic shapes of individual teeth develop as a result from folding of the dental epithelium, several signal molecules including Sonic hedgehog, Bmps-2, 4, 7 and Fgf-4 are expressed specifically in restricted and transient epithelial cell clusters, called enamel knots. We propose that the enamel knots provide positional information for the development of the tooth shape, and that they regulate the growth of tooth cusps. (C) 1996 Academic Press Ltd