Developmentally regulated expression of Netrin‐1 and ‐3 in the embryonic mouse molar tooth germ

Abstract

The Netrins form a small, conserved family of laminin-related signaling proteins regulating axon guidance in the developing nervous system. Here, we analyzed the roles of Netrin-1 and -3 in trigeminal axon guidance to the first lower molar of the embryonic mouse. Netrin-1 showed a restricted epithelial expression domain buccal to the tooth germ, toward which the pioneer tooth axons initially appear to navigate. Later, before birth, transcripts were colocalized with nerve fibers around the bell stage tooth germ. Analysis of Netrin-1-deficient mice, however, did not reveal any obvious disturbances in the axon growth or pattern of tooth innervation. In contrast, Netrin-3 showed a prominent, distinct expression in the axon pathway and target field mesenchyme around the tooth. Hence, it is possible that Netrin-3 may regulate pioneer axon growth toward and within the embryonic tooth target field.

The many faces of semaphorins: from development to pathology

“…Together with involvement in bone development, semaphorins are also important in tooth development. Sema3A, 3B, 3C and 3F as well as their receptors NRP1 and NRP2 exhibit distinct developmentally regulated expression patterns during tooth organogenesis in the embryonic mouse [112]. Sema3A regulates timing of tooth innervation and dental axon navigation and patterning [113].…”

“…Exhibit distinct developmentally regulated expression patterns during tooth organogenesis in the embryonic mouse [112] Cell. Mol.…”

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

“…Similarly, the neural cell adhesion molecule (Ncam) and low-affinity neurotrophin receptor (Lanr), which may sequester neurotrophins, are present in the dental follicle target field during axon navigation (Luukko et al, 1996;Mitsiadis et al, 1992;Obara and Takeda, 1993). In addition, mRNAs for netrin 3 (Net3) are expressed in the mesenchymal axon pathway and dental follicle region and may therefore be involved in the regulation of dental axon growth (Loes et al, 2003). In situ hybridization analysis of the late bud/early stage tooth germs (E14-) revealed no differences between the expression patterns of Ngf, Gdnf, Lanr, Ncam and Net3 in Sema3a -/-and wild-type mice (Fig.…”

Tissue interactions in the regulation of axon pathfinding during tooth morphogenesis

“…Postnatally, both genes are upregulated in the odontoblastic target area of the dental papilla consisting of dentin, predentin, odontoblasts, and the underlying mesenchymal subodontoblastic area before axon ingrowth to the dental papilla (Luukko et al, 1997a, b), though they appear not to initiate axon growth to the dental papilla (Lillesaar et al, 1999). Among the other neuroregulatory molecules implicated in dental axon guidance are Ncam (neural cell adhesion molecule), which appears to mediate contact attraction on growing axons, and secreted Netrin‐3 expressed in dental target fields (Obara and Takeda, 1993; Loes et al, 2003). Cell membrane–bound ephrin ligands and their Eph receptor tyrosine kinases regulate axon guidance by acting as repellants, but they can also function as axonal attractors (Kullander and Klein, 2002).…”