Ectodysplasin regulates activator-inhibitor balance in murine tooth development through Fgf20 signaling

Development. 2012 Sep;139(17):3189-99. doi: 10.1242/dev.079558. Epub 2012 Jul 25.


Uncovering the origin and nature of phenotypic variation within species is the first step in understanding variation between species. Mouse models with altered activities of crucial signal pathways have highlighted many important genes and signal networks regulating the morphogenesis of complex structures, such as teeth. The detailed analyses of these models have indicated that the balanced actions of a few pathways regulating cell behavior modulate the shape and number of teeth. Currently, however, most mouse models studied have had gross alteration of morphology, whereas analyses of more subtle modification of morphology are required to link developmental studies to evolutionary change. Here, we have analyzed a signaling network involving ectodysplasin (Eda) and fibroblast growth factor 20 (Fgf20) that subtly affects tooth morphogenesis. We found that Fgf20 is a major downstream effector of Eda and affects Eda-regulated characteristics of tooth morphogenesis, including the number, size and shape of teeth. Fgf20 function is compensated for by other Fgfs, in particular Fgf9 and Fgf4, and is part of an Fgf signaling loop between epithelium and mesenchyme. We showed that removal of Fgf20 in an Eda gain-of-function mouse model results in an Eda loss-of-function phenotype in terms of reduced tooth complexity and third molar appearance. However, the extra anterior molar, a structure lost during rodent evolution 50 million years ago, was stabilized in these mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution
  • Ectodysplasins / metabolism*
  • Fibroblast Growth Factors / metabolism*
  • Galactosides
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • In Situ Hybridization
  • Indoles
  • Luciferases
  • Mice
  • Microscopy, Confocal
  • Morphogenesis / physiology*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Tooth / embryology*


  • Ectodysplasins
  • Fgf20 protein, mouse
  • Galactosides
  • Indoles
  • Fibroblast Growth Factors
  • Luciferases
  • 5-bromo-4-chloro-3-indolyl beta-galactoside