Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development

Cell. 1993 Oct 8;75(1):45-58.


Growth factor-mediated signaling has been implicated in the regulation of epithelial-mesenchymal interactions during organogenesis. Bone morphogenetic protein 4 (BMP-4), a member of the transforming growth factor beta superfamily, is expressed in the presumptive dental epithelium at the initiation of tooth development. Subsequently, epithelial signaling leads to mesenchymal induction of BMP-4 expression. To address the role of this factor, BMP-4-releasing agarose beads were added to dental mesenchyme in culture. These beads induced a translucent mesenchymal zone similar to that induced by dental epithelium. Moreover, three transcription factors (Msx-1, Msx-2, and Egr-1) whose expression is governed by epithelial signaling were induced in response to BMP-4. In addition, BMP-4 induced its own mesenchymal expression. These findings support the hypothesis that BMP-4 mediates epithelial-mesenchymal interactions during early tooth development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins
  • Cell Division
  • Embryo, Mammalian
  • Epithelium / physiology
  • Gene Expression*
  • Genes, Homeobox*
  • Growth Substances / metabolism*
  • In Situ Hybridization
  • Mesoderm / cytology
  • Mesoderm / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Odontogenesis* / drug effects
  • Protein Biosynthesis
  • Proteins / metabolism*
  • Proteins / pharmacology
  • Recombinant Proteins / pharmacology
  • Signal Transduction


  • Bone Morphogenetic Proteins
  • Growth Substances
  • Proteins
  • Recombinant Proteins