NGF, BDNF, NT3, NT4 AND GDNF IN TOOTH DEVELOPMENT

Neurotrophic factors have robust effects on development, differentiati on, maintenance and regeneration of neurons. In the present study, we have used in situ hybridization to determine the specific sites of gen e activity of five neurotrophic factors during tooth development. Nerv e growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRN As were mainly detected in the dental papilla/pulp in postnatal rats, and the pattern of expression correlated with onset of dental innervat ion. In contrast, neurotrophin 3 (NT3) and 4 (NT4) mRNA expression pat terns were predominantly epithelial and were strongest during early de velopmental stages when teeth are not yet innervated. Glial cell line- derived neurotrophic factor (GDNF) mRNA was present in dental epitheli um at early stages, but later in development, GDNF mRNA expression was mainly mesenchymal and observed in the odontoblast layer and extendin g into the subodontoblast zone. Our results suggest that both neurotro phins and GDNF may have multiple functions during tooth development. I n addition to an influence on the establishment of the dental innervat ion, neurotrophic substances might have morphogenetic effects such as modulating the proliferation or differentiation of developing epitheli al and mesenchymal cells.