A retinoic acid receptor-selective agonist causes jaw deformity in the Japanese flounder, Paralichthys olivaceus
A retinoic acid receptor-selective agonist causes jaw deformity in the Japanese flounder, Paralichthys olivaceus
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DOI：
10.1016/s0044-8486(03)00076-0
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发表时间：
2003-05
期刊：
影响因子：
4.5
通讯作者：
Y. Haga;T. Suzuki;H. Kagechika;T. Takeuchi
中科院分区：
文献类型：
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作者：
Y. Haga;T. Suzuki;H. Kagechika;T. Takeuchi
我们研究了合成维甲酸对牙槽鱼胚胎后发育过程中颌骨发育的影响。用AM80[视黄酸受体α/β选择性视黄酸]和甲基戊二酸[MA，视黄酸X受体选择性视黄酸]处理牙科仔鱼。AM80可引起所有鱼的下颌骨畸形，而MA可引起不到20%的鱼的下颌骨畸形。AM80导致上颌骨和下颌骨严重畸形，而MA不影响上颌骨。对下颌骨的RT-PCR分析表明，AM80处理后RAR的表达显著增加。Am80和MA处理都抑制了Hedgehog家族的受体Patted(PTC)的表达。用抗RARα抗体进行免疫组织化学染色，发现颌骨周围有RARα阳性的成骨细胞。我们认为调节成骨细胞活性的RAR信号通路的紊乱是颌骨畸形的主要原因。
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.