Rapid and Integrative Discovery of Retina Regulatory Molecules
Rapid and Integrative Discovery of Retina Regulatory Molecules
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DOI：
10.1016/j.celrep.2018.07.090
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发表时间：
2018-08-28
期刊：
影响因子：
8.8
通讯作者：
Samuel, Melanie A.
中科院分区：
文献类型：
--
作者：
Albrecht, Nicholas E.;Alevy, Jonathan;Samuel, Melanie A.
视网膜的功能依赖于精确组织的神经元和突触以及适当模式的血管系统来支持它们。这些特征的改变可能会导致视力丧失。然而，由于缺乏快速识别哺乳动物神经元和血管调节因子的方法，我们对视网膜组织途径的了解仍然不完整。在这里，我们开发了一条通过高通量视网膜筛选(Insight)识别神经和突触完整性基因的管道，分析候选表达、血管构型、细胞组织和突触排列。利用这个系统，我们检测了102个突变的小鼠品系，并鉴定了16个独特的视网膜调节基因。这些候选中有15个被确定为新的视网膜调节器，许多(16个中的9个)与人类神经疾病有关。这些结果扩大了视网膜回路组织所涉及的遗传图谱，并为继续发现哺乳动物视网膜调节因子和致病等位基因提供了路线图。
Retinal function relies on precisely organized neurons and synapses and a properly patterned vasculature to support them. Alterations in these features can result in vision loss. However, our understanding of retinal organization pathways remains incomplete because of a lack of methods to rapidly identify neuron and vasculature regulators in mammals. Here we developed a pipeline for the identification of neural and synaptic integrity genes by high-throughput retinal screening (INSiGHT) that analyzes candidate expression, vascular patterning, cellular organization, and synaptic arrangement. Using this system, we examined 102 mutant mouse lines and identified 16 unique retinal regulatory genes. Fifteen of these candidates are identified as novel retina regulators, and many (9 of 16) are associated with human neural diseases. These results expand the genetic landscape involved in retinal circuit organization and provide a road map for continued discovery of mammalian retinal regulators and disease-causing alleles.