Molecular mechanisms of cytodifferentiation in mammalian tooth development

The morphological stages of tooth development-bud, cap, bell, and terminal differentiation-have been known for decades. The past 10 years have seen the elucidation of many of the molecular events driving these morphogenetic stages. Signaling via the fibroblast growth factor (FGF), bone morphogenetic protein (BMP), hedgehog, and wingless protein families and their downstream transcription factors have been identified as key players in the epithelial-mesenchymal signaling loops driving tooth development. Currently the most complete description of the mechanisms in tooth development extends only through the cap stage. The body of work concerning the mechanisms directing the bell and cytodifferentiation stages is growing. This has mainly, but not exclusively, focused on the expression and effects of FGFs and BMPs in these latter stages, and is reviewed here. Additionally, recent results suggest that phenotypic proteins of both ameloblasts and odontoblasts, such as amelogenin and dentin matrix protein 2 may act as the final instructive signals in cytodifferentiation.