Spatial signalling mediated by the transforming growth factor-β signalling pathway during tooth formation

Tooth development relies on sequential and reciprocal interactions between the epithelial and mesenchymal tissues, and it is continuously regulated by a variety of conserved and specific temporal-spatial signalling pathways. It is well known that suspensions of tooth germ cells can form tooth-like structures after losing the positional information provided by the epithelial and mesenchymal tissues. However, the particular stage in which the tooth germ cells start to form tooth-like structures after losing their positional information remains unclear. In this study, we investigated the reassociation of tooth germ cells suspension from different morphological stages during tooth development and the phosphorylation of Smad2/3 in this process. Four tooth morphological stages were designed in this study. The results showed that tooth germ cells formed odontogenic tissue at embryonic day (E) 14.5, which is referred to as the cap stage, and they formed tooth-like structures at E16.5, which is referred to as the early bell stage, and E18.5, which is referred to as the late bell stage. Moreover, the transforming growth factor-β signalling pathway might play a role in this process. The stage at which tooth precursor cells in suspension form tooth-like structures has been determined in rat cells. Xue-Dong Zhou of Sichuan University, China, and colleagues created single-cell preparations from tooth precursor cells at different stages of development, and assessed their ability to form tooth structures when removed from the normal surroundings of tooth development. The results showed that cells 16.5 days old or more formed distinct tooth-like structures including pulp and dentin, while younger cells formed disordered tissue. Cells aged 18.5 days before isolation went on to exhibit partially formed enamel. The researchers suggest the TGF-beta signaling pathway, identified in previous studies as a mediator of tooth formation, may play a role in this setting. The findings warrant further investigation into tooth bioengineering, which may ultimately yield therapies to replace defective teeth in humans.