Cell Autonomous Requirement for TGF-beta Signaling During Odontoblast Differentiation and Dentin Matrix Formation

Mech Dev. 2007 Jul;124(6):409-15. doi: 10.1016/j.mod.2007.02.003. Epub 2007 Mar 12.

Abstract

TGF-beta subtypes are expressed in tissues derived from cranial neural crest cells during early mouse craniofacial development. TGF-beta signaling is critical for mediating epithelial-mesenchymal interactions, including those vital for tooth morphogenesis. However, it remains unclear how TGF-beta signaling contributes to the terminal differentiation of odontoblast and dentin formation during tooth morphogenesis. Towards this end, we generated mice with conditional inactivation of the Tgfbr2 gene in cranial neural crest derived cells. Odontoblast differentiation was substantially delayed in the Tgfbr2(fl/fl);Wnt1-Cre mutant mice at E18.5. Following kidney capsule transplantation, Tgfbr2 mutant tooth germs expressed a reduced level of Col1a1 and Dspp and exhibited defects including decreased dentin thickness and absent dentinal tubules. In addition, the expression of the intermediate filament nestin was decreased in the Tgfbr2 mutant samples. Significantly, exogenous TGF-beta2 induced nestin and Dspp expression in dental pulp cells in the developing tooth organ. Our data suggest that TGF-beta signaling controls odontoblast maturation and dentin formation during tooth morphogenesis.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Dentin / cytology
  • Dentin / growth & development*
  • Integrases / genetics
  • Mice
  • Mice, Transgenic
  • Odontoblasts / cytology*
  • Signal Transduction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology*
  • Wnt1 Protein / genetics

Substances

  • Transforming Growth Factor beta
  • Wnt1 Protein
  • Cre recombinase
  • Integrases