Department of Basic and Clinical Neuroscience, King's College London, London, SE5 9NU, UK.
Champalimaud Research, Champalimaud Foundation, Av. Brasília, Lisbon, 1400-038, Portugal.
F1000Res. 2020 May 1;9:317. doi: 10.12688/f1000research.23154.2. eCollection 2020.
Invertebrate glia performs most of the key functions controlled by mammalian glia in the nervous system and provides an ideal model for genetic studies of glial functions. To study the influence of adult glial cells in ageing we have performed a genetic screen in using a collection of transgenic lines providing conditional expression of micro-RNAs (miRNAs). Here, we describe a methodological algorithm to identify and rank genes that are candidate to be targeted by miRNAs that shorten lifespan when expressed in adult glia. We have used four different databases for miRNA target prediction in but find little agreement between them, overall. However, top candidate gene analysis shows potential to identify essential genes involved in adult glial functions. One example from our top candidates' analysis is ( ). We establish that is necessary in many glial cell types, that it affects motor behaviour and, at the sub-cellular level, is responsible for defects in cellular membranes, autophagy and mitochondria quality control. We also verify the remarkable conservation of functions between and its mammalian orthologue, GBF1, validating the use of as an alternative 3Rs-beneficial model to knock-out mice for studying the biology of GBF1, potentially involved in human neurodegenerative diseases.
无脊椎动物神经胶质细胞执行了哺乳动物神经胶质细胞在神经系统中控制的大部分关键功能，并为神经胶质细胞功能的遗传研究提供了理想的模型。为了研究成年神经胶质细胞在衰老过程中的影响，我们利用提供微 RNA（miRNA）条件表达的转基因系集合，在 中进行了遗传筛选。在这里，我们描述了一种方法学算法，用于鉴定和排序候选基因，这些候选基因可能是在成年神经胶质细胞中表达时会缩短寿命的 miRNA 的靶标。我们在 中使用了四个不同的 miRNA 靶标预测数据库，但总体上发现它们之间的一致性很小。然而，顶级候选基因分析显示出有可能识别参与成年神经胶质细胞功能的必需基因。我们的顶级候选基因分析的一个例子是 （ ）。我们确定 是许多神经胶质细胞类型所必需的，它会影响运动行为，并且在亚细胞水平上，它会导致细胞膜、自噬和线粒体质量控制缺陷。我们还验证了 与其哺乳动物同源物 GBF1 之间功能的显著保守性，这验证了使用 作为敲除小鼠的替代 3Rs-有益模型来研究潜在参与人类神经退行性疾病的 GBF1 生物学的有效性。
