Sox2+ progenitors in sharks link taste development with the evolution of regenerative teeth from denticles

Abstract

Teeth and denticles belong to a specialized class of mineralizing epithelial appendages called odontodes. Although homology of oral teeth in jawed vertebrates is well supported, the evolutionary origin of teeth and their relationship with other odontode types is less clear. We compared the cellular and molecular mechanisms directing development of teeth and skin denticles in sharks, where both odontode types are retained. We show that teeth and denticles are deeply homologous developmental modules with equivalent underlying odontode gene regulatory networks (GRNs). Notably, the expression of the epithelial progenitor and stem cell marker sex-determining region Y-related box 2 (sox2) was tooth-specific and this correlates with notable differences in odontode regenerative ability. Whereas shark teeth retain the ancestral gnathostome character of continuous successional regeneration, new denticles arise only asynchronously with growth or after wounding. Sox2+ putative stem cells associated with the shark dental lamina (DL) emerge from a field of epithelial progenitors shared with anteriormost taste buds, before establishing within slow-cycling cell niches at the (i) superficial taste/tooth junction (T/TJ), and (ii) deep successional lamina (SL) where tooth regeneration initiates. Furthermore, during regeneration, cells from the superficial T/TJ migrate into the SL and contribute to new teeth, demonstrating persistent contribution of taste-associated progenitors to tooth regeneration in vivo. This data suggests a trajectory for tooth evolution involving cooption of the odontode GRN from nonregenerating denticles by sox2+ progenitors native to the oral taste epithelium, facilitating the evolution of a novel regenerative module of odontodes in the mouth of early jawed vertebrates: the teeth.regeneration | stem cells | odontogenesis | chondrichthyes | evolutionary novelty

Spatially restricted dental regeneration drives pufferfish beak development

“…The generation of new teeth requires a source of epithelial progenitors (16,17). To maintain this ability, polyphyodonts must retain a population of these cells throughout life.…”

“…To maintain this ability, polyphyodonts must retain a population of these cells throughout life. Epithelial dental progenitors have been localized to the dental lamina in polyphyodonts (7,8,16,17,20), with the microenvironment maintaining these cells in an otherwise dynamic and proliferative system. Pufferfishes regenerate and replace their teeth intraosseously, within the dental cavity (12).…”

“…Given that epithelial progenitors are required for dental regeneration to take place (4), it is unclear where these cells reside in pufferfishes, because the developing teeth remain separated from the oral epithelium by an osteodentine casing fused to the jaw. Here, we define tooth regeneration as the de novo cyclical formation of tooth units from a defined epithelial dental lamina that must be continuously maintained by a progenitor cell niche (17). In this context, and for clarity, the term "tooth replacement" refers to the structural formation and positional replacement of tooth units, whereas the term "tooth regeneration" refers to the developmental process by which teeth are replaced, i.e., through the maintenance of a progenitor-rich epithelial dental lamina for de novo tooth production.…”

“…The role of the dental lamina in the regeneration of teeth is well understood (2,16,17). Sox2 (Sex-determining region Y-box 2) is a transcription factor known for its role in maintaining cell pluripotency and stem cell renewal (23).…”

“…Sox2 (Sex-determining region Y-box 2) is a transcription factor known for its role in maintaining cell pluripotency and stem cell renewal (23). It is expressed in epithelial dental progenitors in the dental lamina of all polyphyodont vertebrates (2,4,16,17) and is thought to regulate dental progenitor cell state (16). Therefore we investigated its expression during pufferfish tooth formation to determine the location of epithelial dental progenitors in pufferfishes.…”