Traf6 is essential for murine tooth cusp morphogenesis

Dev Dyn. 2004 Jan;229(1):131-5. doi: 10.1002/dvdy.10400.


Ectodermal appendages such as skin, hair, teeth, and sweat glands are affected in patients with hypohidrotic (anhydrotic) ectodermal dysplasia (HED). It has been established that mutations in the tumor necrosis factor (TNF) superfamily of molecules, i.e., ectodysplasin (EDA), EDA receptor (EDAR), and EDAR-associated death domain (EDARADD; the intracellular adaptor for EDAR), are responsible for several forms of HED in humans and mice. We show here by in situ hybridisation that another TNF family (orphan) receptor, TROY (also known TAJ, TAJ-alpha, TRADE, and TNFRSF19), is strongly coexpressed with Edar in the epithelial enamel knot signalling centres that are believe to regulate cuspal morphogenesis during murine tooth development. Traf6 is known to function as an intracellular adaptor protein for Troy and examination of Traf6 mutant mice revealed abnormalities in molar teeth that are similar but more severe than those produced by mutations in Eda signalling molecules. This finding suggests that, in additional to ectodysplasin, another TNF pathway involving Troy/Traf6 is involved in molar tooth cusp formation and identifies an essential role for a Traf in tooth development. Developmental Dynamics 229:131-135, 2004.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA, Complementary / genetics
  • Dental Enamel / embryology
  • Ectodermal Dysplasia / embryology
  • Ectodermal Dysplasia / genetics
  • Ectodysplasins
  • Gene Expression Regulation, Developmental
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mice
  • Mice, Mutant Strains
  • Molar / abnormalities
  • Molar / embryology
  • Mutation
  • Odontogenesis / genetics
  • Odontogenesis / physiology*
  • Phenotype
  • Proteins / genetics
  • Proteins / physiology*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology
  • TNF Receptor-Associated Factor 6


  • DNA, Complementary
  • EDA protein, human
  • Ectodysplasins
  • Eda protein, mouse
  • Membrane Proteins
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • TNF Receptor-Associated Factor 6
  • Tnfrsf19 protein, mouse