Inhibition of apoptosis in the primary enamel knot does not affect specific tooth crown morphogenesis in the mouse

Int J Dev Biol. 2000 Jun;44(4):389-96.


The enamel knot (EK), located in the center of cap-stage tooth germs, is a transitory cluster of non-dividing epithelial cells, eventually linked to the outer dental epithelium by the enamel septum (ES). It might act as a signaling center providing positional information for tooth morphogenesis and could regulate the growth of tooth cusps through the induction of secondary signaling EKs. The EK undergoes apoptosis, which could constitute a mechanism whereby the signaling functions of this structure are terminated. Recently, we demonstrated the segregation of 5-bromo-2'-deoxyuridine (BrdU) negative inner dental epithelial (IDE) cells of the EK into as many individual groups of cells as cusps will form and suggested a morphogenetic role for these particular IDE cells. Using Z-VAD-fmk, a specific caspase inhibitor, apoptosis in the primary EK of first mouse lower cap-staged molars and lower incisors cultured in vitro was abrogated. No obvious histological alterations were observed in the incisors, whereas a prominent EK and an ES connecting the outer dental epithelium (ODE) and the BrdU negative IDE cells capping cusp L2 were observed in the molars. EK specific transcription (Shh, Msx-2, Bmp-2, Bmp-4) was down-regulated in the body of these structures with the exception of the associated IDE cells. In these experimental conditions, segregation of non-dividing transcriptionally active IDE cells occurred and a normal cusp pattern was expressed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / genetics
  • Bromodeoxyuridine / metabolism
  • DNA-Binding Proteins / genetics
  • Dental Enamel / cytology
  • Dental Enamel / embryology*
  • Dental Enamel / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Homeodomain Proteins
  • Image Processing, Computer-Assisted
  • In Situ Hybridization
  • In Vitro Techniques
  • Mice
  • Mice, Inbred ICR
  • Odontogenesis* / genetics
  • Pregnancy
  • Proteins / genetics
  • Trans-Activators*
  • Transforming Growth Factor beta*


  • Bmp2 protein, mouse
  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Hedgehog Proteins
  • Homeodomain Proteins
  • MSX2 protein
  • Proteins
  • Trans-Activators
  • Transforming Growth Factor beta
  • Bromodeoxyuridine