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 Sema3aexpression 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 Msx1transcription 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.

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The treatment outcome of 55 root perforations in man were related to pretreatment conditions and various treatment procedures used, with a mean recall period of 3 years 5 months. In this study maxillary teeth were perforated three times more often (74.5 per cent) than mandibular teeth (25.5 per cent); 47 per cent of the perforations were due to endodontic and 53 per cent due to prosthodontic treatment. The buccal and mesial root surfaces as well as the midroot areas were most often perforated. In 25 per cent, radiographic changes were directly related to the perforated areas. Twenty-eight perforations were repaired by orthograde fillings with gutta-percha and Kloro-percha N-phi; eight received a combined orthograde and surgical repair, and in only three cases a surgical approach was used. Four cases received no treatment but were recalled, and twelve perforations showed a size and location hopeless for repair; the teeth were therefore extracted. Five failures of the primary orthograde treatment group later underwent surgical treatment and were followed up for 3 years 3 months. The overall success rate in the primary treatment group of teeth was 56 per cent while 36 per cent became failures. Five failures were retreated, and four of these became successful. A combined orthograde and surgical repair of the perforations provided the most favourable outcome with 92 per cent successful. The study stresses the importance of preventing this type of treatment complication.

Wnt signaling is essential for tooth formation. Members of the Dickkopf (Dkk) family modulate the Wnt signaling pathway by binding to the Wnt receptor complex. Comparison of Dkk1, -2, and -3 mRNA expression during mouse tooth formation revealed that all three genes showed distinct spatiotemporally regulated expression patterns. Dkk1 was prominently expressed in the distal, incisor-bearing mesenchyme area of the mandibular process during the initial stages of tooth formation. During molar morphogenesis Dkk1 was detected in the dental mesenchyme, including the preodontoblasts. Dkk2 was seen in the dental papilla, whereas Dkk3 was specifically expressed in the putative epithelial signaling centers, the primary and secondary enamel knots. Postnatally, Dkk1 was prominently expressed in the preodonto-and odontoblasts, while Dkk3 mRNAs were transiently seen in the preameloblasts before the onset of enamel matrix secretion. These results suggest that modulation of Wnt-signaling by Dkks may serve important functions in patterning of dentition as well as in crown morphogenesis and dental hard-tissue formation. Developmental Dynamics 233:161-166, 2005.

Like many other organs, the tooth develops as a result of the epithelial-mesenchymal interactions. In addition, the tooth is a well-defined peripheral target organ for sensory trigeminal nerves, which are required for the function and protection of the teeth. Dental trigeminal axon growth and patterning are tightly linked with advancing tooth morphogenesis and cell differentiation. This review summarizes recent findings on the regulation of dental axon pathfinding, which have provided evidence that the development of tooth trigeminal innervation is controlled by epithelial-mesenchymal interactions. The early dental epithelium possesses the information to instruct tooth nerve supply, and signals mediating these interactions are part of the signaling networks regulating tooth morphogenesis. Tissue interactions, thus, appear to provide a central mechanism of spatiotemporally orchestrating tooth formation and dental axon navigation and patterning. Developmental Dynamics 234:482-488, 2005.