Williams Charles H, Hong Charles C
Department of Cell and Developmental Biology, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Methods Mol Biol. 2015;1263:167-74. doi: 10.1007/978-1-4939-2269-7_13.
Major developmental pathways play critical roles in wide array of human pathologies. Chemical genomic screening allows for the discovery of novel tools not only to target known pathway interactors but also to discover new, chemically tractable targets for known pathways. The zebrafish has emerged as a useful model for developmental biology and has been well characterized. The zebrafish represents a hardy conglomerate of totipotent cells that are massively and simultaneously assessing all significant pathways in parallel in an endogenous context. This represents a gold standard for biological assays, chemically targeting select pathways without causing pleiotropic effects. Here, we describe methods used to develop high content screening assays implementing transgenic zebrafish to assess phenotypic changes that have identified several classes of novel compounds that effect developmental pathways.
主要的发育途径在众多人类疾病中起着关键作用。化学基因组筛选不仅能够发现针对已知途径相互作用分子的新型工具，还能为已知途径发现新的、化学上易于处理的靶点。斑马鱼已成为发育生物学中一种有用的模型，并且其特征已得到充分描述。斑马鱼代表了一群全能细胞的集合体，这些细胞在内源环境中大规模地同时并行评估所有重要途径。这代表了生物测定的金标准，即化学靶向特定途径而不产生多效性影响。在这里，我们描述了用于开发高内涵筛选测定的方法，这些方法利用转基因斑马鱼来评估表型变化，从而鉴定出了几类影响发育途径的新型化合物。
