the presence of nerves is an important factor in successful organ regeneration in amphibians. the Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called coMBi and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. the induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. our results suggest that the role of nerves is conserved and that fgf+Bmp signals play key roles in axolotl organ-level regeneration. the presence of nerves is an important factor in successful organ regeneration in amphibians. the Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called coMBi and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. the induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. our results suggest that the role of nerves is conserved and that fgf+Bmp signals play key roles in axolotl organ-level regeneration. The ability to regenerate lost tissues or organs in human patients has long been eagerly desired. Teeth are among the organs for which a novel treatment allowing perfect regeneration would be extremely useful. Due to the unique and multifarious roles of the teeth and associated structures, there has been a sustained effort to find optimal ways to replace missing dentition over many centuries. Amphibian teeth have unique physiological features but maintain some structural and functional similarities to mammalian teeth 1,2. One of the most notable features of amphibian teeth is polyphyodonty. Through polyphyodonty, amphibians replace their teeth continuously during life, whereas each mammalian tooth has either one or two generations (mono-or diphyodonty). Amphibian tooth development has been described in some classic studies 3-10. As far as we know, Hertwig published the first study of amphibian tooth development 5. Recently, the literature on tooth regeneration in amphibians was reviewed 1. The dental lamina is induced from the oral epithelium. The dental lamina, which consists of two layers, invades into the oral mesenchyme. The distal region of the dental lamina interacts with mesenchymal cells and forms a cup that is composed of the outer dental epithelium and the inner dental epithelium. The inner dental epithelium differentiates into enamel organs. The mesenchymal ...