Specialized stem cell niche enables repetitive renewal of alligator teeth

Proc Natl Acad Sci U S A. 2013 May 28;110(22):E2009-18. doi: 10.1073/pnas.1213202110. Epub 2013 May 13.


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.

Keywords: Wnt; placode; regeneration; slow cycling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alligators and Crocodiles
  • Animals
  • Bromodeoxyuridine
  • Cell Proliferation
  • Glycoproteins / metabolism
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins
  • Models, Animal*
  • Models, Biological*
  • Odontogenesis / physiology*
  • Regeneration / physiology*
  • Signal Transduction / physiology*
  • Stem Cells / physiology*
  • Tenascin / metabolism
  • Tooth / cytology
  • Tooth / physiology*
  • X-Ray Microtomography
  • beta Catenin / metabolism


  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • Tenascin
  • WD repeat containing planar cell polarity effector
  • beta Catenin
  • Bromodeoxyuridine