Cao Sha-Sha, Jia Wen-Shuang, Zhao Qing-Shun
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210061, China.
Yi Chuan. 2012 Sep;34(9):1159-64.
Retinoic acid (RA) plays essential roles in vertebrate embryogenesis. However, vertebrates cannot synthesize RA de novo. They synthesize it by two oxidative steps, first converting the precursor vitamin A into retinal by retinol dehydrogenase, and then oxidizing retinal into RA irreversibly by retinal dehydrogenase. It is known that vitamin A deficiency (VAD) causes Vitamin A Deficiency Syndrome in animals including quail, mouse, rat, and human. However, little is known about the effects of VAD on zebrafish embryogenesis. In this study, we obtained zebrafish VAD embryos from the zebrafish fed a retinoids-free diet. By analyzing the VAD embryos, we found that VAD caused asymmetric somitogenesis and abnormal hindbrain patterning in zebrafish embryos. However, the phenotype of defected hindbrain in VAD embryos was not as severe as that in the embryos in which aldh1a2, the major gene that is responsible for RA synthesis in zebrafish early development, was knocked down, or the embryos treated with 10 mmol/L DEAB (diethylaminobenzaldehyde, inhibitor of retinal dehydrogenases). Our results indicated that the VAD embryos were short of but not free of vitamin A, and they might also have a RA generation pathway independent of retinal dehydrogenase.
视黄酸（RA）在脊椎动物胚胎发育过程中发挥着至关重要的作用。然而，脊椎动物无法从头合成RA。它们通过两个氧化步骤来合成RA，首先由视黄醇脱氢酶将前体维生素A转化为视黄醛，然后由视黄醛脱氢酶将视黄醛不可逆地氧化为RA。已知维生素A缺乏症（VAD）会在包括鹌鹑、小鼠、大鼠和人类在内的动物中引发维生素A缺乏综合征。然而，关于VAD对斑马鱼胚胎发育的影响却知之甚少。在本研究中，我们从喂食无类维生素A饮食的斑马鱼中获得了斑马鱼VAD胚胎。通过分析VAD胚胎，我们发现VAD会导致斑马鱼胚胎出现不对称体节发生和后脑模式异常。然而，VAD胚胎中后脑缺陷的表型并不像在斑马鱼早期发育中负责RA合成的主要基因aldh1a2被敲除的胚胎，或用10 mmol/L二乙氨基苯甲醛（DEAB，视黄醛脱氢酶抑制剂）处理的胚胎那样严重。我们的结果表明，VAD胚胎缺乏但并非完全没有维生素A，并且它们可能还存在一条独立于视黄醛脱氢酶的RA生成途径。
