Affecting tooth morphology and renewal by fine-tuning the signals mediating cell and tissue interactions.

Interactions between the epithelial and mesenchymal tissue components of developing teeth regulate morphogenesis and cell differentiation, and determine key features of dentitions and individual teeth such as the number, size, shape and formation of dental hard tissues. Tissue interactions are mediated by signal molecules belonging mostly to four conserved families: transforming growth factor (TGF)beta, Wnt, fibroblast growth factor (FGF) and Hedgehog. Recent work from our laboratory has demonstrated that tooth morphology and the capacity of the teeth to grow and renew can be affected by tinkering with these signal pathways in transgenic mice. The continuous growth of the mouse incisors, as well as their subdivision into the crown and root domains, is dramatically altered by modulating a network of FGF and two TGFbeta signals, bone morphogenetic protein (BMP) and Activin. This network is responsible for the regulation of the maintenance, proliferation and differentiation of epithelial stem cells that are responsible for growth and enamel production. On the other hand, the activation of the Wnt signalling pathway induces continuous renewal of mouse teeth (which normally are not replaced), resembling tooth replacement in other vertebrates. It can be concluded that the different dental characters are quite flexible and that they are regulated by the same conserved signal pathways. These findings support the suggestions that tinkering with the signal pathways is the key mechanism underlying the morphological evolution of teeth as well as other organs.