STIMULATION OF MURINE TOOTH DEVELOPMENT IN ORGANOTYPIC CULTURE BY THENEUROTRANSMITTER SEROTONIN

Serotonin (5-hydroxytryptamine; 5-HT) uptake sites are transiently exp ressed in craniofacial epithelia and mesenchyme, including the tooth g erm, during mouse embryogenesis. Based on malformations and patterns o f cell proliferation and death in cultured mouse embryos exposed to 5- HT uptake inhibitors, it has been hypothesized that 5-HT acts as a dos e-dependent morphogenetic signal for craniofacial development. The pre sent study was designed to investigate the effect of 5-HT on tooth-ger m formation in serum-free mandibular explant cultures prepared from em bryonic day-13 (plug day = embryonic day-1) mouse embryos. In the abse nce of serum or a 5-HT supplement, tooth germs develop only to the bud stage in these cultures. When explants were cultured for 8 days in a defined medium supplemented with 5-HT, late bell-stage tooth germs wer e stimulated to develop in a dose-dependent manner. This effect was re versed by addition of the 5-HT uptake inhibitor fluoxetine. Anti-5-HT immunocytochemistry demonstrated specific uptake of 5-HT by developing tooth germ and mandibular epithelium, which could also be blocked by fluoxetine. These results suggest that 5-HT may regulate dental differ entiation, and that intracellular uptake is required for this action.