Abstract
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.
Highlights
The presence of nerves is an important factor in successful organ regeneration in amphibians
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
Dentine and predentine are deposited between the ameloblast layer, which is differentiated from the inner dental epithelium, and the odontoblasts
Summary
The presence of nerves is an important factor in successful organ regeneration in amphibians. The teeth formed two distinct positions within the tooth alignment: they can be attached to the paired bones of the lower jaw (dentaries and coronoids, functional tooth), or they can remain detached from the jaw bones, in which case they are lost (non-functional teeth). Tooth buds are induced from the inner layer of the buccal epithelium, i.e., the dental lamina. Previous reports have strongly suggested that tooth bud regeneration depends on the residual lamina in the stump region[13,14,15]. While these experimental descriptions represented a thorough investigating for their time, tooth regeneration has not been revisited with current biological technologies. Our results reveal the molecular mechanisms underlying tooth regeneration in axolotls, which may be applicable to other vertebrates
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