Molecular genetics of tooth morphogenesis and patterning: the right shape in the right place

Development of the mammalian tooth has for many years served as a useful model system for the study of cell-cell interactions in organogenesis. Early development of teeth (tooth buds) shows many morphological and molecular similarities with early development of other organs such as the lung, hair, kidney, etc. There has been much progress toward understanding epithelial/mesenchymal cell signaling in tooth germ formation. Advances in understanding the formation of different shapes of teeth (morphogenesis) at their correct positions in the jaws (patterning) has, until recently, been less forthcoming. We review here the latest ideas on the control of odontogenic patterning and morphogenesis. The stages of early tooth development are well-defined histologically and have been described in numerous textbooks. The progression from localized thickenings of oral epithelium to bud, cap, and bell stages provides an adequate description of the gross morphological changes seen in the epithelial cells of early developing tooth germs. Less obvious are the concomitant changes taking place in the dental (ecto)mesenchymal cells which originate from the cranial neural crest and which condense around the tooth bud epithelium. However, it is very clear that these mesenchymal cells are equal partners with epithelium during the early stages of tooth germ formation and undergo complex changes which, although not obvious histologically, are revealed with molecular (gene) probes. Genes identified as being important for the early communication between the epithelial and ectomesenchymal cells mainly comprise those which code for proteins which act as secreted signals between the cells (ligands) and those that code for nuclear proteins that act to control gene expression in response to the signals. Little is presently known about the changes in structural proteins such as cell adhesion molecules which are involved in mediating the physical interactions between cells and generating the morphological changes.