Retinal Wnt signaling defect in a zebrafish fetal alcohol spectrum disorder model.
Retinal Wnt signaling defect in a zebrafish fetal alcohol spectrum disorder model.
复制标题
斑马鱼胎儿酒精谱系障碍模型中的视网膜Wnt信号缺陷。
DOI：
10.1371/journal.pone.0201659
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Marrs JA
中科院分区：
文献类型：
--
作者：
Muralidharan P;Sarmah S;Marrs JA
由产前酒精暴露引起的胎儿酒精谱系障碍包括眼部异常（小眼球、感光器功能障碍、白内障）。斑马鱼胚胎从原肠胚形成到体节发生暴露于乙醇，表现出严重的眼部缺陷，包括小眼症和感光细胞分化缺陷。乙醇处理的斑马鱼有一个扩大的睫状边缘区（CMZ）相对于视网膜的大小和减少米勒神经胶质细胞（MGCs）。乙醇暴露产生不成熟的感光细胞增殖增加，表明细胞周期退出失败。胚胎期乙醇暴露对CMZ中的信号机制产生影响，包括CMZ中的Wnt信号、Notch信号和neurod基因表达。维甲酸或叶酸与乙醇的共补充挽救了Wnt信号传导和视网膜分化。使用GSK 3抑制剂（LSN 2105786; Eli Lilly and Co.）修复了视网膜细胞分化途径。用Wnt激动剂处理暴露于乙醇的胚胎，其拯救CMZ中的Wnt活性细胞、视网膜中的Notch活性细胞、增殖和感光体末端分化。我们的研究结果说明了Wnt信号在乙醇诱导的视网膜缺陷中的关键作用。
Fetal alcohol spectrum disorder caused by prenatal alcohol exposure includes ocular abnormalities (microphthalmia, photoreceptor dysfunction, cataracts). Zebrafish embryos exposed to ethanol from gastrulation through somitogenesis show severe ocular defects, including microphthalmia and photoreceptor differentiation defects. Ethanol-treated zebrafish had an enlarged ciliary marginal zone (CMZ) relative to the retina size and reduced Müller glial cells (MGCs). Ethanol exposure produced immature photoreceptors with increased proliferation, indicating cell cycle exit failure. Signaling mechanisms in the CMZ were affected by embryonic ethanol exposure, including Wnt signaling in the CMZ, Notch signaling and neurod gene expression. Retinoic acid or folic acid co-supplementation with ethanol rescued Wnt signaling and retinal differentiation. Activating Wnt signaling using GSK3 inhibitor (LSN 2105786; Eli Lilly and Co.) restored retinal cell differentiation pathways. Ethanol exposed embryos were treated with Wnt agonist, which rescued Wnt-active cells in the CMZ, Notch-active cells in the retina, proliferation, and photoreceptor terminal differentiation. Our results illustrate the critical role of Wnt signaling in ethanol-induced retinal defects.
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影响因子：
2.9
作者：
Bilotta, J;Barnett, JA;Saszik, S
通讯作者：
Saszik, S
DOI：
10.1111/j.1530-0277.2011.01511.x
发表时间：
2011-09
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Kashyap B;Frey RA;Stenkamp DL
通讯作者：
Stenkamp DL
影响因子：
5.3
作者：
Bernardos, Rebecca L.;Barthel, Linda K.;Raymond, Pamela A.
通讯作者：
Raymond, Pamela A.
DOI：
10.3791/1229
发表时间：
2009-03-25
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Brend, Tim;Holley, Scott A
通讯作者：
Holley, Scott A
影响因子：
1.6
作者：
Hug, TE;Fitzgerald, KM;Cibis, GW
通讯作者：
Cibis, GW