Although there are times when we may wish our teeth lacked nerves, these nerves are required for the function and protection of our teeth. On p. , Kettunen and co-workers reveal that the expression of semaphorin 3a (Sema3a), a secreted repulsive axon guidance molecule, coordinates axon navigation and patterning with the formation of the first mandibular molar in mice. First, the researchers use knockout mice to show that Sema3a is essential for early tooth innervation. Then, in tissue recombination experiments, they show that Wnt4 expressed by early oral and dental epithelium induces Sema3aexpression in the molar mesenchyme before the first nerve fibres arrive. Later on during the axon navigation of dental pioneer nerves, Wnt4 and Tgfβ1 together control Sema3a expression in the dental mesenchyme. Thus,epithelial-mesenchymal interactions in developing teeth provide the instructions for the formation of their nerve supply.
