Organized Emergence of Multiple-Generations of Teeth in Snakes Is Dysregulated by Activation of Wnt/Beta-Catenin Signalling

Abstract

In contrast to mammals, most reptiles constantly regenerate their teeth. In the snake, the epithelial dental lamina ends in a successional lamina, which proliferates and elongates forming multiple tooth generations, all linked by a permanent dental lamina. To investigate the mechanisms used to control the initiation of new tooth germs in an ordered sequential pattern we utilized the polyphodont (multiple-generation) corn snake (Pantherophis guttatus). We observed that the dental lamina expressed the transcription factor Sox2, a multipotent stem cell marker, whereas the successional lamina cells expressed the transcription factor Lef1, a Wnt/β-catenin pathway target gene. Activation of the Wnt/β-catenin pathway in culture increased the number of developing tooth germs, in comparison to control untreated cultures. These additional tooth germs budded off from ectopic positions along the dental lamina, rather than in an ordered sequence from the successional lamina. Wnt/β-catenin activation enhanced cell proliferation, particularly in normally non-odontogenic regions of the dental lamina, which widely expressed Lef1, restricting the Sox2 domain. This suggests an expansion of the successional lamina at the expense of the dental lamina. Activation of the Wnt/β-catenin pathway in cultured snake dental organs, therefore, led to changes in proliferation and to the molecular pattern of the dental lamina, resulting in loss of the organised emergence of tooth germs. These results suggest that epithelial compartments are critical for the arrangement of organs that develop in sequence, and highlight the role of Wnt/β-catenin signalling in such processes.

Evolution and developmental diversity of tooth regeneration

“…Similar to the chondrichthyan and amphibian species studied, the replacing series of tooth germs in polyphyodont squamates are united by a permanent dental lamina linking the developing teeth in a chain to the functional dentition, and the oral surface [10,12,47,48]. At birth 3-4 developing generations of teeth are found linked to the dental lamina, making a developmental series ready to replace the functional tooth.…”

“…The squamate successional lamina is a region of high proliferation and low apoptosis (programmed cell death) [47,56]. Fate mapping of the successional lamina in the snake has shown that the cells in the successional lamina contribute both to the new generations of teeth and are retained at the tip of the lamina [10]. In species that only have one set of teeth the successional lamina forms but stops proliferating, losing its bulge shape.…”

“…These issues with current developmental models have led to a recent surge in studies focused on natural tooth replacement in a variety of polyphodont and diphyodont (two sets of teeth) species [10][11][12][13][14]. The timing of this increase in research could not have come at a better time -now any organism is accessible as a potential model for developmental biology given our current advanced genomic, cellular and developmental technologies.…”

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

“…Many reptiles, such as geckos and crocodiles, most toothed fishes and other vertebrates are polyphyodont (Fuenzalida et al 2000;Gaete and Tucker 2013). Most mammals are diphyodont, such as our species, but others (e.g., elephants, kangaroos and manatees) are polyphyodont.…”

“…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)]. …”