Evc regulates a symmetrical response to Shh signaling in molar development

J Dent Res. 2013 Mar;92(3):222-8. doi: 10.1177/0022034512471826. Epub 2013 Jan 11.

Abstract

Tooth morphogenesis involves patterning through the activity of epithelial signaling centers that, among other molecules, secrete Sonic hedgehog (Shh). While it is known that Shh responding cells need intact primary cilia for signal transduction, the roles of individual cilia components for tooth morphogenesis are poorly understood. The clinical features of individuals with Ellis-van Creveld syndrome include various dental anomalies, and we show here that absence of the cilial protein Evc in mice causes various hypo- and hyperplasia defects during molar development. During first molar development, the response to Shh signaling is progressively lost in Evc-deficient embryos and, unexpectedly, the response consistently disappears in a buccal to lingual direction. The important role of Evc for establishing the buccal-lingual axis of the developing first molar is also supported by a displaced activity of the Wnt pathway in Evc mutants. The observed growth abnormalities eventually manifest in first molar microdontia, disruption of molar segmentation and symmetry, root fusions, and delayed differentiation. Analysis of our data indicates that both spatially and temporally disrupted activities of the Shh pathway are the primary cause for the variable dental anomalies seen in patients with Ellis-van Creveld syndrome or Weyers acrodental dysostosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Cilia
  • Hedgehog Proteins / physiology*
  • Image Processing, Computer-Assisted
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molar / growth & development*
  • Odontogenesis / genetics*
  • Signal Transduction
  • Tooth Abnormalities / genetics*
  • Tooth Eruption / genetics
  • Tooth Eruption / physiology*
  • Wnt Signaling Pathway / physiology

Substances

  • Evc protein, mouse
  • Hedgehog Proteins
  • Membrane Proteins
  • Shh protein, mouse