Cellular and molecular basis of cadmium-induced deformities in zebrafish embryos
Cellular and molecular basis of cadmium-induced deformities in zebrafish embryos
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DOI：
10.1002/etc.5620191223
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发表时间：
2000-12-01
影响因子：
4.1
通讯作者：
Wu, RSS
中科院分区：
文献类型：
--
作者：
Cheng, SH;Wai, AWK;Wu, RSS
已知镉会导致多种脊椎动物发育缺陷，但对其潜在的分子机制知之甚少。在这项研究中，我们使用斑马鱼（Danio rerio）胚胎作为模型系统来研究镉引起的毒性。受精后5小时收集的受精胚胎在含有1至1,000μM CdCl2的培养基中孵育18小时。中位胚胎致死浓度 (LC50) 为 168 μM，而总不良反应（死亡和发育缺陷）的中位效应浓度 (EC50) 为 138 μM。观察到六种主要类型的畸形：头部和眼睛发育不全、色素沉着不足、心脏水肿、卵黄囊异常、轴曲度改变和尾部畸形。畸形的发生率随着镉浓度的增加而增加。使用抗肌球蛋白抗体 MF-20 研究了轴曲率改变的胚胎体节。据我们所知，这项研究首次证明了镉引起的脊柱畸形中肌节的形成减少了。使用抗神经组织抗体 zns-2 对头部和眼睛发育不全的胚胎进行了研究，结果发现中枢神经系统发育不良。头部和眼睛发育不全与声波刺猬基因表达缺乏有关，该基因控制神经管和体节的模式。参与尾部形成的基因，例如evenskipped 1和no tail，在尾部畸形的胚胎中异位表达。我们的数据支持这样的假设：镉诱导的鱼类胚胎畸形可能是通过发育调节基因的异位表达介导的。
Cadmium is known to cause developmental defects in a variety of vertebrate species, but relatively little is known about the underlying molecular mechanisms. In this study, we used zebrafish (Danio rerio) embryos as a model system to investigate cadmium-induced toxicities. Fertilized embryos collected at 5-h after fertilization were incubated for 18 h in culture media containing 1 to 1,000 muM CdCl2. The median embryolethal concentration (LC50) was 168 muM, whereas the median effect concentration (EC50) for total adverse effect (mortality and developmental defects) was 138 muM. Six major types of deformities were observed: head and eye hypoplasia, hypopigmentation, cardiac edema, yolk sac abnormalities, altered axial curvature, and tail malformations. The frequency of malformations increased with cadmium concentration. Somites of embryos with altered axial curvature were investigated using the antimyosin antibody MF-20. This study demonstrated, to our knowledge for the first time, reduced myotome formation in cadmium-induced spinal deformity. Embryos with head and eye hypoplasia were studied using the anti-neural tissue antibody zns-2, and a poorly developed central nervous system was revealed. Head and eye hypoplasia were associated with lack of expression of the sonic hedgehog gene, which controls the patterning of the neural tube and somites. Genes involved in tail formations, such as evenskipped 1 and no tail, were ectopically expressed in embryos with tail malformations. Our data support the hypothesis that fish embryonic malformations induced by cadmium might be mediated through ectopic expression of developmental regulatory genes.