Developmentally regulated expression of Sema3A chemorepellant in the developing mouse incisor

Abstract

The expression patterns of Sema3A indicate that it may control the timing and patterning of the incisor innervation. In particular, Sema3A appears to regulate innervation of the periodontal ligament, while nerve penetration into the incisor dental pulp appears not to be dependent on Sema3A. Moreover, Sema3A may regulate the functions of cervical loops and the development of alveolar bone. Future study with Sema3A deficient mice will help to elucidate the putative neuronal and non-neuronal functions of Sema3A in incisor tooth development.

Integration of tooth morphogenesis and innervation by local tissue interactions, signaling networks, and semaphorin 3A

“…Similarly, in the single-rooted incisor tooth germ, Sema3 transcripts are lacking in the pulp/root areas through which nerves navigate the pulp. 7,23,26,45 Analyses of Sema3A-deficient transgenic mice confirmed that SEMA3A is a critical regulator of tooth innervation, that is serially exploited at critical embryonic and postnatal stages of tooth innervation. 23,25,26 In both Sema3A-deficient incisor and molar tooth germs, pioneer axons reach the tooth germ prematurely and show apparent disturbances in nerve patterning and fasciculation.…”

“…25 In contrast, the innervation of the dental pulp in Sema3A ¡/¡ incisors appears normal, reflecting the finding that Sema3A is largely nonexistent in the postnatal incisor pulp. 26,45 However, an abnormal, elevated number of axons and their arborization, is observed in the incisor periodontium, particularly at the labial side. 26 The finding that some degree of correction occurred in the dental nerve patterning of Sema3A ¡/¡ molars 25 suggests that other neuro-regulatory molecules may compensate for the lack of SEMA3A signaling.…”

“…38,39,40,41,42,43 mRNAs for SEMA3A, which repels both sensory and sympathetic nerves, 41 displays developmentally regulated and distinct cellular expression patterns in both epithelial and mesenchymal tissue during mouse molar and incisor development. 23,26,44,45 Sema3A is specifically expressed in sites that are devoid of navigating axons, suggesting functions in tooth innervation. During the onset of tooth formation and innervation, Sema3A is expressed in the dental and jaw mesenchyme areas, adjacent to the pioneer nerve branch (the trigeminal 'molar nerve') growing toward the early tooth germ.…”

“…Later, during the bud, cap and bell stages, Sema3A is seen around the tooth germ, flanking the mesenchymal dental follicle target area, where the number of nerves gradually increases in both embryonic and postnatal molar and incisor tooth germs. 7,23,26,45 In the dental pulp, although Sema3A is located in the middle part of the base of the 2-rooted mandibular molar tooth, transcripts are specifically absent from the future sites of the mesial and distal roots where nerve fibers grow into the dental pulp. Similarly, in the single-rooted incisor tooth germ, Sema3 transcripts are lacking in the pulp/root areas through which nerves navigate the pulp.…”

“…3 Spatio-temporal changes in the Sema3A expression domain in the incisor and molar tooth germs, especially in the early dental mesenchymal compartments, correlated with inductive signaling between the dental epithelium and mesenchyme. 23,45 Analyses of Sema3A regulation using organotypic cultures and tissue separation, and recombination experiments, demonstrated that rather than being controlled by, or being dependent on, peripheral nerves, mesenchymal Sema3A expression was instead regulated by the dental epithelium during early tooth development. 23 Thus, these results demonstrated, for the very first time, that local tissue interactions regulate mesenchymal Sema3A expression, and thereby the development of the sensory nerve supply in the tooth germ.…”