BLOCKADE OF THE INITIATION OF MURINE ODONTOGENESIS IN-VITRO BY CITRAL, AN INHIBITOR OF ENDOGENOUS RETINOIC ACID SYNTHESIS

Endogenous retinoids are present in the embryonic mouse mandible and r each a concentration peak immediately before the formation of the dent al lamina. Because exogenous retinoids alter the pattern of the dental lamina and the expression of epidermal growth factor mRNA (a transcri pt necessary for initiation of odontogenesis), the role of retinoic ac id in the initiation of odontogenesis was studied here. Citral (3,7-di methyl-2,6-octadienal), a known inhibitor of retinoic acid synthesis, was used to block the endogenous synthesis of retinoic acid in the mou se embryonic mandible before the formation of the dental lamina (gesta tional day 9). A 24-h exposure to citral totally blocked tooth formati on in 7/10 mandibles. Reductions of endogenous retinoic acid concentra tions were confirmed by high-performance liquid chromatography. Tooth formation was restored by simultaneous treatment with all-trans retino ic acid or 9-cis retinoic acid during the citral exposures (first 24 h of culture). Endogenous retinoic acid is necessary for the initiation of odontogenesis.