Mouse rudimentary diastema tooth primordia are devoid of peripheral nerve fibers.

The tooth is a well-defined peripheral target organ for trigeminal nerve fibers. However, only limited information is available regarding pioneer axon guidance to the developing tooth target field. In rodents there is a toothless diastema region between incisors and molars that in the mouse maxilla contains three rudimentary tooth anlagen. Their development stop at the early bud stage when the primary nerve axons grow towards the developing first molar tooth germs. In order to provide background information for studies of regulatory mechanisms of pioneer axon guidance to the developing tooth germs, we investigated the distribution of nerve fibers in the mouse diastema tooth buds, and compared it to the axon growth to the maxillary and mandibular first molar tooth germs by immunohistochemical localization of peripherin and PGP9.5. Analysis of serial sections showed that trigeminal nerve fibers emerging from the trigeminal maxillary and mandibular nerve trunks started to grow towards the developing molar tooth germ at the early bud stage, and subsequently they diverged into buccal and lingual branches next to the condensed dental mesenchyme. During the cap stage, nerve fibers were observed around the tooth germ in the dental follicle region. In contrast, no nerve fibers were located in the vicinity of the diastema tooth primordia at any stage studied, nor did any nerve fibers appear to grow towards this region. Our results show that the development and subsequent disappearance of the diastema tooth primordia takes place without peripheral trigeminal innervation. The diastema tooth primordia may therefore be a useful model system for future studies on molecular regulatory mechanisms of pioneer axon guidance to the tooth germs, and possibly also for evolutionary studies of peripheral axon guidance mechanisms.