Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects
Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects
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DOI：
10.1242/bio.20135546
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发表时间：
2013-10-15
期刊：
影响因子：
2.4
通讯作者：
Marrs, James A.
中科院分区：
文献类型：
--
作者：
Sarmah, Swapnalee;Muralidharan, Pooja;Marrs, James A.
当怀孕的母亲饮酒时，会发生胎儿酒精谱系障碍 (FASD)，导致胚胎乙醇暴露和特征性出生缺陷，包括颅面、神经和心脏缺陷。原肠胚形成是对致畸剂暴露特别敏感的发育阶段，斑马鱼是研究原肠胚形成和胎儿酒精谱系障碍（FASD）的杰出模型。外延（卵裂球细胞在卵黄细胞上扩散）、弦前板迁移和会聚/伸展细胞运动对早期乙醇暴露敏感。在此，提出了表征乙醇对外泌体和原肠胚形成的毒性机制的实验。脱落机制包括卵裂球径向嵌入细胞运动和卵黄细胞微管细胞骨架将胚胎拉至植物极。这两个过程都因乙醇暴露而中断。乙醇对细胞迁移的影响也表明细胞粘附受到影响，这通过细胞聚集测定得到证实。 E-钙粘蛋白细胞粘附分子的表达不受乙醇暴露的影响，但控制外泌体和原肠胚形成的E-钙粘蛋白分布发生了变化。 E-钙粘蛋白在卵裂球中重新分布到细胞质聚集体中，并在胚胎外卵黄细胞中显着重新分布。基因表达微阵列分析用于识别早期发育缺陷的潜在致病因素，在乙醇暴露的胚胎中，控制表观代谢的细胞粘附分子原钙粘蛋白-18a (pcdh18a) 的表达显着降低。在乙醇处理的胚胎中注射 pcdh18a 合成 mRNA 部分挽救了表皮细胞运动，包括包膜层细胞形状的变化。总之，数据表明，乙醇诱导的外胚层形成和原肠胚形成缺陷是多因素的，包括卵黄细胞（胚胎外组织）微管细胞骨架破坏和卵裂球粘附缺陷，部分原因是 pcdh18a 表达减少。 (C) 2013。由 The Company of Biologies Ltd 出版。这是一篇根据知识共享署名许可条款分发的开放获取文章。
Fetal alcohol spectrum disorder (FASD) occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell), prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented that characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression was not affected by ethanol exposure, but E-cadherin distribution, which controls epiboly and gastrulation, was changed. E-cadherin was redistributed into cytoplasmic aggregates in blastomeres and dramatically redistributed in the extraembryonic yolk cell. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a), which controls epiboly, was significantly reduced in ethanol exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue) microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression. (C) 2013. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.