BMP-SHH signaling network controls epithelial stem cell fate via regulation of its niche in the developing tooth

Dev Cell. 2015 Apr 20;33(2):125-35. doi: 10.1016/j.devcel.2015.02.021. Epub 2015 Apr 9.


During embryogenesis, ectodermal stem cells adopt different fates and form diverse ectodermal organs, such as teeth, hair follicles, mammary glands, and salivary glands. Interestingly, these ectodermal organs differ in their tissue homeostasis, which leads to differential abilities for continuous growth postnatally. Mouse molars lose the ability to grow continuously, whereas incisors retain this ability. In this study, we found that a BMP-Smad4-SHH-Gli1 signaling network may provide a niche supporting transient Sox2+ dental epithelial stem cells in mouse molars. This mechanism also plays a role in continuously growing mouse incisors. The differential fate of epithelial stem cells in mouse molars and incisors is controlled by this BMP/SHH signaling network, which partially accounts for the different postnatal growth potential of molars and incisors. Collectively, our study highlights the importance of crosstalk between two signaling pathways, BMP and SHH, in regulating the fate of epithelial stem cells during organogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Proliferation
  • Epithelial Cells / cytology
  • Gene Expression Regulation, Developmental
  • Glycosyltransferases / biosynthesis
  • Hedgehog Proteins / metabolism*
  • Incisor / embryology
  • Incisor / growth & development*
  • Incisor / metabolism
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Molar / embryology
  • Molar / growth & development*
  • Molar / metabolism
  • Odontogenesis*
  • Receptor, Notch1 / biosynthesis
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction
  • Smad4 Protein / genetics
  • Smad4 Protein / metabolism*
  • Stem Cells / cytology
  • Zinc Finger Protein GLI1


  • Bone Morphogenetic Proteins
  • Gli1 protein, mouse
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Notch1 protein, mouse
  • Receptor, Notch1
  • SOXB1 Transcription Factors
  • Shh protein, mouse
  • Smad4 Protein
  • Smad4 protein, mouse
  • Sox2 protein, mouse
  • Zinc Finger Protein GLI1
  • Glycosyltransferases
  • Lfng protein, mouse