Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin signaling

Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18627-32. doi: 10.1073/pnas.0607289103. Epub 2006 Nov 22.

Abstract

The single replacement from milk teeth to permanent teeth makes mammalian teeth different from teeth of most nonmammalian vertebrates and other epithelial organs such as hair and feathers, whose continuous replacement has been linked to Wnt signaling. Here we show that mouse tooth buds expressing stabilized beta-catenin in epithelium give rise to dozens of teeth. The molar crowns, however, are typically simplified unicusped cones. We demonstrate that the supernumerary teeth develop by a renewal process where new signaling centers, the enamel knots, bud off from the existing dental epithelium. The basic aspects of the unlocked tooth renewal can be reproduced with a computer model on tooth development by increasing the intrinsic level of activator production, supporting the role of beta-catenin pathway as an upstream activator of enamel knot formation. These results may implicate Wnt signaling in tooth renewal, a capacity that was all but lost when mammals evolved progressively more complicated tooth shapes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Heterozygote
  • Mice
  • Mice, Transgenic
  • Mouth Mucosa / metabolism*
  • Mouth Mucosa / physiology
  • Mutation
  • Signal Transduction / physiology*
  • Tissue Culture Techniques
  • Tooth / embryology
  • Tooth / growth & development*
  • Tooth / metabolism
  • Wnt Proteins / metabolism
  • Wnt Proteins / physiology*
  • beta Catenin / genetics
  • beta Catenin / metabolism
  • beta Catenin / physiology*

Substances

  • Wnt Proteins
  • beta Catenin