Retionic acid and its receptors are required for expression of aryl hydrocarbon receptor mRNA and embryonic development of blood vessel and bone in the medaka fish, Oryzias latipes
Retionic acid and its receptors are required for expression of aryl hydrocarbon receptor mRNA and embryonic development of blood vessel and bone in the medaka fish, Oryzias latipes
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DOI：
10.2108/zsj.21.541
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发表时间：
2004-05-01
影响因子：
0.9
通讯作者：
Yamashita, I
中科院分区：
文献类型：
--
作者：
Hayashida, Y;Kawamura, T;Yamashita, I
视黄酸（RA）是维生素A的活性衍生物，对脊椎动物的正常胚胎发育至关重要，因为RA的缺乏和过量都会导致发育畸形。我们之前报道过芳烃受体（AHR）也需要通过调节细胞色素P450的表达来形成血管和骨。然而，关于维甲酸受体（RAR）和类维甲酸X受体（RXR）在血管胚胎发育中的作用以及RAR/RXR和AHR之间的分子交叉对话，我们知之甚少。我们首次报道了RA和RAR/RXR是AHR mRNA表达和血管和骨的胚胎发育所必需的。RA合成抑制剂（二乙胺苯甲醛）、RAR拮抗剂（Ro41-5253）和RXR拮抗剂（Ro71-4595）、AHR激动剂（α -萘黄酮）和拮抗剂（α -萘黄酮）以及过量RA均能特异性抑制medaka鱼的胚胎器官发生。这些试剂对今后阐明水母胚胎形成过程中血管和骨形成的分子机制具有重要意义。我们的研究结果还表明，medaka胚胎可能有助于筛选血管形成抑制剂，用于抗癌药物。
Retinoic acid (RA), the active derivative of vitamin A, is essential for normal embryonic development of vertebrates because both the lack and excess of RA result in developmental malformations. We previously reported that aryl hydrocarbon receptor (AHR) is also required for vascular and bone formation by regulating cytochrome P450 expression. However, little is known about the roles of retinoic acid receptors (RAR) and retinoid X receptors (RXR) in the embryonic development of blood vessels and molecular cross-talk between RAR/RXR and AHR. We report for the first time that RA and RAR/RXR are required for expression of AHR mRNA and the embryonic development of blood vessel and bone. The embryonic organogenesis of medaka fish was specifically inhibited by an inhibitor of RA synthesis (diethylaminobenzaldehyde), antagonists of RAR (Ro41-5253) and RXR (Ro71-4595), agonist (beta-naphthoflavone) and antagonist (alpha-naphthoflavone) of AHR, and excess RA. These reagents are useful for future studies to elucidate molecular mechanisms for vascular and bone formation in the medaka embryogenesis. Our results also show that medaka embryos may be useful for screening inhibitors of vascular formation for anti-cancer drugs.