Maia Lorena A, Velloso Ian, Abreu Jose G
a Institute of Biomedical Sciences , Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
Expert Opin Drug Discov. 2017 Nov;12(11):1153-1159. doi: 10.1080/17460441.2017.1367281. Epub 2017 Aug 28.
Understanding embryogenesis currently relies largely on the control of gene expression via several signaling pathways. Many of the embryonic signaling pathways guiding embryological events are implicated in diseases that lack effective cure or treatment. Because of the large number and size of the eggs, the rapid development of the embryos and the fact they are amenable to pharmacological, surgical and genetic techniques, Xenopus laevis has been successfully used in searching for compounds that target embryonic signaling pathways. Areas covered: Here, the authors address the use of amphibian eggs/embryos in successful chemical screenings; egg extracts as well as embryo phenotypes have been assayed to reveal drug toxicology effects and novel compounds acting in the Wnt/β-catenin signaling pathway. They do not discuss the use of Xenopus oocyte two-electrode voltage clamps or genome editing tools as approaches for drug discovery because they have been discussed elsewhere. Expert opinion: While high-throughput screening is commonly performed in egg extracts, the embryo axes perturbation system is more suited to the refinement and/or the validation of drug discovery targeting embryonic signaling (particularly the Wnt/β-catenin pathway). In addition, Xenopus has also been used in FETAX (frog embryo teratogenesis assay: Xenopus) to address chemical toxic/teratogenic effects. However, further studies are necessary.
目前,对胚胎发生的理解在很大程度上依赖于通过几种信号通路对基因表达的控制。许多指导胚胎学事件的胚胎信号通路都与缺乏有效治愈方法或治疗手段的疾病有关。由于非洲爪蟾的卵数量多、体积大,胚胎发育迅速,且适合采用药理学、外科手术和遗传学技术,因此它已成功用于寻找靶向胚胎信号通路的化合物。涵盖领域:在此,作者探讨了两栖类卵/胚胎在成功的化学筛选中的应用;对卵提取物以及胚胎表型进行了检测,以揭示药物毒理学效应以及作用于Wnt/β-连环蛋白信号通路的新型化合物。他们没有讨论将非洲爪蟾卵母细胞双电极电压钳或基因组编辑工具用作药物发现方法,因为这些内容已在其他地方进行过讨论。专家观点:虽然高通量筛选通常在卵提取物中进行,但胚胎轴扰动系统更适合于针对胚胎信号(特别是Wnt/β-连环蛋白通路)的药物发现的优化和/或验证。此外,非洲爪蟾也已用于FETAX(蛙胚胎致畸试验:非洲爪蟾)以研究化学物质的毒性/致畸效应。然而,还需要进一步的研究。