Tooth morphogenesis in vivo, in vitro, and in silico

One of the aims of developmental biology is to understand how a single egg cell gives rise to the complex spatial distributions of cell types and extracellular components of the adult phenotype. This review discusses the main genetic and epigenetic interactions known to play a role in tooth development and how they can be integrated into coherent models. Along the same lines, several hypotheses about aspects of tooth development that are currently not well understood are evaluated. This is done from their morphological consequences from the model and how these fit known morphological variation and change during tooth development. Thus the aim of this review is two-fold. On one hand the model and its comparison with experimental evidence will be used to outline our current understanding about tooth morphogenesis. On the other hand these same comparisons will be used to introduce a computational model that makes accurate predictions on three-dimensional morphology and patterns of gene expression by implementing cell signaling, proliferation and mechanical interactions between cells. In comparison with many other models of development this model includes reaction-diffusion-like dynamics confined to a diffusion chamber (the developing tooth) that changes in shape in three-dimensions over time. These changes are due to mechanical interactions between cells triggered by the proliferation enhancing effect of the reactants (growth factors). In general, tooth morphogenesis can be understood from the indirect cross-regulation between extracellular signals, the local regulation of proliferation and differentiation rates by these signals and the effect of intermediate developing morphology on the diffusion, dilution, and spatial distribution of these signals. Overall, this review should be interesting to either readers interested in the mechanistic bases of tooth morphogenesis, without necessarily being interested in modeling per se, and readers interested in development modeling in general.