Touching a nerve in tooth development

Three-dimensional reconstruction of Sema3a (in red) expression in PN1 first molar tooth germ shown from below

Kettunen P, Loes S, Furmanek T, Fjeld K, Kvinnsland IH, ... Luukko K. (2005) Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfß1 regulate semaphorin 3a expression in the dental mesenchyme. Development. 2005 132:323-334.

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 Sema3a expression 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, epithelialmesenchymal interactions in developing teeth provide the instructions for the formation of their nerve supply.