Specialized stem cell niche enables repetitive renewal of alligator teeth

Abstract

Reptiles and fish have robust regenerative powers for tooth renewal. However, extant mammals can either renew their teeth one time (diphyodont dentition) or not at all (monophyodont dentition). Humans replace their milk teeth with permanent teeth and then lose their ability for tooth renewal. Here, we study tooth renewal in a crocodilian model, the American alligator, which has well-organized teeth similar to mammals but can still undergo life-long renewal. Each alligator tooth is a complex family unit composed of the functional tooth, successional tooth, and dental lamina. Using multiple mitotic labeling, we map putative stem cells to the distal enlarged bulge of the dental lamina that contains quiescent odontogenic progenitors that can be activated during physiological exfoliation or artificial extraction. Tooth cycle initiation correlates with β-catenin activation and soluble frizzled-related protein 1 disappearance in the bulge. The dermal niche adjacent to the dermal lamina dynamically expresses neural cell adhesion molecule, tenascin-C, and other molecules. Furthermore, in development, asymmetric β-catenin localization leads to the formation of a heterochronous and complex tooth family unit configuration. Understanding how these signaling molecules interact in tooth development in this model may help us to learn how to stimulate growth of adult teeth in mammals.Wnt | placode | slow cycling | regeneration

Evolution and developmental diversity of tooth regeneration

“…During development in the Nile crocodile the dental lamina extends out from the forming functional tooth and replacement tooth formation can be observed, mimicking the process in squamates [52]. However, at later stages in crocodilians the dental lamina appears to lose its connection to the oral surface and to the functional tooth it will replace, while still remaining connected longitudinally to the dental lamina along the jaw [46]. Thus connection between the dental lamina and the overlying oral epithelium does not appear necessary for its function in these animals.…”

“…In contrast, in polyphyodont reptile species the teeth are generally attached to the jaw bones by either a pleurodont or thecodont attachment. A thecodont attachment is observed in the crocodilia, and is characterised by having the tooth sitting in a socket attached to the bone via a fibrous connection [46]. In the acrodonta there appears to be a trade-off between the advantage of a firmly attached tooth and the ability to replace the teeth.…”

“…In fanged snakes this series of replacement teeth is even longer, with approximately eight teeth ready to place the fangs [49], similar to the number of replacement teeth observed in the chondrichthyans. In the crocodilia, only one developing replacement tooth is observed behind the functional tooth, and together with the dental lamina they form a family unit [46]. This smaller number of tooth germs developing along the dental lamina at any one time may relate to the speed of replacement.…”

“…The end of the crocodilian dental lamina forms a bulge, which enlarges at the start of initiation of the next replacement tooth. The dental lamina then splits from this replacement tooth as it progresses to differentiation [46]. In the squamata and crocodilia, like the amphibia, the replacement teeth form on the lingual side of the functional tooth.…”

Aging of perennial cells and organ parts according to the programmed aging paradigm

“…In cases where the duration had been greater, the solution would have been as easy as is clearly indicated in many species, in which increased tooth wear requires a more or less rapid renewal of teeth. The elephant has six dentitions (Shoshani 2000), and alligators can replace up to 50 times their teeth (Wu et al 2013): The number of replacements is specific enough for the duration of their lives. Other species with strong wear have multiple substitutions, unlimited in their number (Fuenzalida et al 2000;Gaete and Tucker 2013), or they exhibit a continuous growth of the teeth as they wear out [e.g., rodents (Single et al 2001)].…”