ABSTRACT

Helsinki, FIN-00014 Helsinki, Finland Most organs form from epithelial and mesenchymal components, and reciprocal interactions between the two tissues constitute a central regulatory mechanism of epithelial morphogenesis. The growth of the epithelium as well as the folding and branching of epithelial sheets determine the shape of the organs. During recent years, it has become evident that the molecular mechanisms of developmental regulation have been conserved to a great extent during evolution and that similar signaling pathways regulate the morphogenesis of different organs. In this paper we review recent data demonstrating the roles of different signals, such as bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs) and Sonic hedgehog, in the regulation of tooth morphogenesis. We present our results demonstrating the presence of a signaling center in the tooth germ, the enamel knot, which is a transient epithelial structure expressing Bmps, Fgfs and Sonic hedgehog. Finally, we discuss our results showing that apoptosis is developmentally regulated in the epithelial cells, including the enamel knot, during tooth morphogenesis, and that apoptosis can be inhibited by epidermal growth factor (EGF) and FGF. A general role for programmed cell death in silencing embryonic signaling centers is suggested.