A retinoic acid receptor-selective agonist causes jaw deformity in the Japanese flounder, Paralichthys olivaceus

We examined the effects of synthetic retinoids on the jaw development of Japanese flounder during postembryonic development. Flounder larvae were exposed to Am80 [a retinoic acid receptor (RAR)α/β-selective retinoid] and methoprene acid [MA, a retinoid X receptor (RXR)-selective retinoid]. Am80 induced lower jaw deformities in all fish, whereas MA induced lower jaw deformities in less than 20% of the fish. Am80 caused drastic deformities in the upper jaw as well as the lower jaw, while MA did not affect the upper jaw. RT-PCR analysis of the lower jaw revealed that RAR expression was greatly increased by Am80 treatment. Expression of patched (ptc) which is a receptor of the hedgehog family, was inhibited by both Am80 and MA treatments. Immunohistochemistry using anti-RARα-antibody revealed that RARα-positive osteoblasts exist around the jaw bones. We propose that disturbance of the RAR signaling pathway regulating osteoblast activity is mainly responsible for the jaw deformities.