Coordination of trigeminal axon navigation and patterning with tooth organ formation: Epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfβ1 regulate semaphorin 3a expression in the dental mesenchyme

Pälvi Kettunen, Sigbjørn Løes, Tomasz Furmanek, Karianne Fjeld, Inger Hals Kvinnsland, Oded Behar, Takeshi Yagi, Hajime Fujisawa, Seppo Vainio, Masahiko Taniguchi, Keijo Luukko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

During development, trigeminal nerve fibers navigate and establish their axonal projections to the developing tooth in a highly spatiotemporally controlled manner. By analyzing Sema3a and its receptor Npn1 knockout mouse embryos, we found that Sema3a regulates dental trigeminal axon navigation and patterning, as well as the timing of the first mandibular molar innervation, and that the effects of Sema3a appear to be mediated by Npn1 present in the axons. By performing tissue recombinant experiments and analyzing the effects of signaling molecules, we found that early oral and dental epithelia, which instruct tooth formation, and epithelial Wnt4 induce Sema3a expression in the presumptive dental mesenchyme before the arrival of the first dental nerve fibers. Later, at the bud stage, epithelial Wnt4 and Tgfβ1 regulate Sema3a expression in the dental mesenchyme. In addition, Wnt4 stimulates mesenchymal expression of Msx1 transcription factor, which is essential for tooth formation, and Tgfβ1 proliferation of the dental mesenchymal cells. Thus, epithelial-mesenchymal interactions control Sema3a expression and may coordinate axon navigation and patterning with tooth formation. Moreover, our results suggest that the odontogenic epithelium possesses the instructive information to control the formation of tooth nerve supply.

Original languageAmerican English
Pages (from-to)323-334
Number of pages12
JournalJournal of Embryology and Experimental Morphology
Volume132
Issue number2
DOIs
StatePublished - Jan 2005

Keywords

  • Axon growth
  • Mouse
  • Odontogenesis
  • Tissue interactions
  • Tooth

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