Fig. 8. Schematic model for coordination of early tooth organogenesis and establishment of nerve supply by epithelial-mesenchymal interactions. The Sema3a exclusion areas (in red) regulate timing of tooth innervation and the innervation pattern. Prior to the histological onset of tooth formation (E10.5), the odontogenic oral epithelium, which instructs tooth formation and also possesses information to control tooth-specific nerve supply, induces (mediated by Wnt4) Sema3a in the presumptive dental mesenchyme. During subsequent morphogenesis epithelial signaling and Wnt4 and Tgfß1 continue to control Sema3a expression domains in the dental mesenchyme target area. Wnt4 and Tgfß1 contribute to the regulation of tooth morphogenesis by maintaining Msx1 (the effect of Wnt4 on Msx1 expression at E11.5 is hypothetical) and stimulating dental mesenchymal cell proliferation, respectively. The trigeminal molar nerve located in the mesenchymal axon pathway and tooth target fields are indicated in black.