CELLULAR EXPRESSION OF NEUROTROPHIN MESSENGER-RNAS DURING TOOTH DEVELOPMENT

Target-derived neurotrophins support and sustain peripheral sensory ne urons during development. In addition, it has been suggested that thes e growth factors could have developmental functions in non-neuronal ti ssues. To further elucidate the possible roles of neurotrophins in too th morphogenesis and innervation, we have used in-situ hybridization t o determine the specific sites of neurotrophin gene activity in pre-an d postnatal rat jaws from E16 to P7. All four neurotrophins were expre ssed during tooth development with specific temporospatial patterns. N erve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNAs were mainly detected in the dental papilla/pulp in postnatal ani mals, and the pattern of expression correlated with the onset of denta l innervation. In contrast, neurotrophin 3 (NT3) and neurotrophin 4 (N T4) mRNA expression patterns were predominantly epithelial and were st rongest during early developmental stages when teeth are not yet inner vated. Dental papilla NGF-mRNA expression was first seen in both epith elium and mesenchyme and later shifted to the odontoblast layer and th e subodontoblast zone. BDNF-mRNA labeling was present in low levels in the early dental organ, but increased in the pulp and in the odontobl ast cell layer of the developing teeth at later developmental stages. Both NT3 and NT4 mRNA were observed in the prenatal oral epithelium an d the inner dental epithelium. NT3-mRNA labeling was seen mainly in th e cervical loop region, fissure system depressions and cuspal tops, wh ile NT4 mRNA was more evenly distributed in the dental epithelium. At P7, NT3-mRNA labeling was below detection level and NT4 mRNA expressio n was lower than at prior stages. Complementary to reports on the pres ence of low-affinity neurotrophin receptor (LANR), trkB and trkC mRNA in the developing teeth, our results suggest that neurotrophins may ha ve multiple functions during tooth morphogenesis. Neurotrophins might participate in epithelial-mesenchymal interactions in early tooth morp hogenetic events such as proliferation and differentiation of epitheli al and mesenchymal cells. In addition, based on mRNA localization in p ostnatal animals, we also suggest that NGF and BDNF (beside glial cell line-derived neurotrophic factor) might participate in establishing a nd maintaining the innervation of the teeth, thus acting as classical neurotrophic factors.