An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination.
An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination.
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DOI：
10.7554/elife.35136
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发表时间：
2018-07-06
期刊：
影响因子：
7.7
通讯作者：
Lyons DA
中科院分区：
文献类型：
--
作者：
Early JJ;Cole KL;Williamson JM;Swire M;Kamadurai H;Muskavitch M;Lyons DA
髓鞘少突胶质细胞对中枢神经系统（CNS）的形成和功能至关重要。它们的破坏与许多神经发育、神经精神和神经退行性疾病有关。然而，最近的研究表明，少突胶质细胞可能易于治疗疾病。近年来，斑马鱼已成为研究髓鞘少突胶质细胞生物学和药物发现的良好对象。在这里，通过将斑马鱼幼虫自动递送到旋转盘共聚焦显微镜，我们能够在体内自动实现髓鞘少突胶质细胞的高分辨率成像。从那里，我们开发了一个图像分析管道，促进筛选具有表观遗传和翻译后靶点的化合物，以调节髓鞘少突胶质细胞的数量。该筛选确定了在体内强烈促进髓鞘少突胶质细胞形成的新化合物。我们的成像平台和分析管道是灵活的，可以用于使用斑马鱼的高分辨率成像屏幕。
Myelinating oligodendrocytes are essential for central nervous system (CNS) formation and function. Their disruption is implicated in numerous neurodevelopmental, neuropsychiatric and neurodegenerative disorders. However, recent studies have indicated that oligodendrocytes may be tractable for treatment of disease. In recent years, zebrafish have become well established for the study of myelinating oligodendrocyte biology and drug discovery in vivo. Here, by automating the delivery of zebrafish larvae to a spinning disk confocal microscope, we were able to automate high-resolution imaging of myelinating oligodendrocytes in vivo. From there, we developed an image analysis pipeline that facilitated a screen of compounds with epigenetic and post-translational targets for their effects on regulating myelinating oligodendrocyte number. This screen identified novel compounds that strongly promote myelinating oligodendrocyte formation in vivo. Our imaging platform and analysis pipeline is flexible and can be employed for high-resolution imaging-based screens of broad interest using zebrafish.