Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling

Dev Cell. 2006 Aug;11(2):181-90. doi: 10.1016/j.devcel.2006.05.014.

Abstract

Unlike humans, who have a continuous row of teeth, mice have only molars and incisors separated by a toothless region called a diastema. Although tooth buds form in the embryonic diastema, they regress and do not develop into teeth. Here, we identify members of the Sprouty (Spry) family, which encode negative feedback regulators of fibroblast growth factor (FGF) and other receptor tyrosine kinase signaling, as genes that repress diastema tooth development. We show that different Sprouty genes are deployed in different tissue compartments--Spry2 in epithelium and Spry4 in mesenchyme--to prevent diastema tooth formation. We provide genetic evidence that they function to ensure that diastema tooth buds are refractory to signaling via FGF ligands that are present in the region and thus prevent these buds from engaging in the FGF-mediated bidirectional signaling between epithelium and mesenchyme that normally sustains tooth development.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Diastema / embryology*
  • Epithelium / drug effects
  • Epithelium / physiology
  • Fibroblast Growth Factors / antagonists & inhibitors*
  • Fibroblast Growth Factors / physiology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mesoderm / drug effects
  • Mesoderm / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / pharmacology
  • Nerve Tissue Proteins / physiology*
  • Protein-Serine-Threonine Kinases
  • Proteins / genetics
  • Proteins / pharmacology
  • Proteins / physiology*
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Tooth / embryology*
  • Tooth / growth & development

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Proteins
  • Spry4 protein, mouse
  • Fibroblast Growth Factors
  • Protein-Serine-Threonine Kinases
  • Spry2 protein, mouse