REGULATION BY SEROTONIN OF TOOTH-GERM MORPHOGENESIS AND GENE-EXPRESSION IN MOUSE MANDIBULAR EXPLANT CULTURES

Serotonin (5-HT) stimulates tooth-germ development in embryonic mouse mandibular explant cultures, but it is not clear whether this is due t o a direct action on epithelial-mesenchymal interactions, or whether d evelopment was stimulated indirectly by serotonergic regulation of oth er morphoregulatory molecules. A calcium-binding protein, S-100 beta, and the extracellular-matrix molecule, tenascin, two molecules thought to be important in craniofacial development, together with cartilage proteoglycan core protein, a marker for chondrogenesis, are modulated by serotonergic ligands in mandibular micromass cultures. Here, it was demonstrated that 5-HT stimulates expression of cartilage proteoglyca n core protein, and inhibits expression of S-100 beta and tenascin in mandibular explants. Further, ondansetron (Zofran), a 5-HT3 receptor a ntagonist, and NAN-190, a 5-HT1A antagonist, reversed the serotonergic stimulation of core protein and tooth germ development. In contrast s erotonergic modulation of S-100 beta and tenascin expression was not r eversed by any of the 5-HT receptor antagonists tested, although the 5 -HT uptake inhibitor, fluoxetine, did reverse the effect of 5-HT on S- 100 beta expression, as well as tooth-germ development. These results support previous work suggesting that 5-HT plays an important part in craniofacial development, especially in dentinogenesis and chondrogene sis. However, the possibility that tenascin or S-100 beta mediate the effects of 5-HT on tooth-germ development is not supported. Rather, th ese results raise the possibility that 5-HT may exert effects directly on tooth-germ morphogenesis mediated by intracellular uptake of 5-HT and/or activation of 5-HT1A and 5-HT3 receptors. (C) 1998 Elsevier Sci ence Ltd. All rights reserved.