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First published online 16 December 2004
doi: 10.1242/dev.01541

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Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfß1 regulate semaphorin 3a expression in the dental mesenchyme

¹ Division of Anatomy and Cell Biology, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway
² Department of Experimental Medicine and Cancer Research, The Hebrew University, Jerusalem, 91120, Israel
³ Laboratories of Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan
⁴ Group of Developmental Neurobiology, Division of Biological Science, Nagoya University Graduate School of Science, Chikusa-ku, Nagoya, 464-8602, Japan
⁵ Biocenter Oulu and Department of Biochemistry, Faculties of Science and Medicine, University of Oulu, 90014, Finland
⁶ Department of Biochemistry and Molecular Biology, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

^* Author for correspondence (e-mail: keijo.luukko{at}pki.uib.no)

Accepted 20 October 2004

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 Tgfß1 regulate Sema3a expression in the dental mesenchyme. In addition, Wnt4 stimulates mesenchymal expression of Msx1 transcription factor, which is essential for tooth formation, and Tgfß1 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.

Key words: Odontogenesis, Tissue interactions, Tooth, Axon growth, Mouse

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