Mariano Vittoria, Achsel Tilmann, Bagni Claudia, Kanellopoulos Alexandros K
Department of Fundamental Neurosciences, University of Lausanne, Lausanne 1005, Switzerland; Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
Department of Fundamental Neurosciences, University of Lausanne, Lausanne 1005, Switzerland.
Neuroscience. 2020 Oct 1;445:12-30. doi: 10.1016/j.neuroscience.2020.07.034. Epub 2020 Jul 28.
Neurodevelopmental disorders (NDDs) include a large number of conditions such as Fragile X syndrome, autism spectrum disorders and Down syndrome, among others. They are characterized by limitations in adaptive and social behaviors, as well as intellectual disability (ID). Whole-exome and whole-genome sequencing studies have highlighted a large number of NDD/ID risk genes. To dissect the genetic causes and underlying biological pathways, in vivo experimental validation of the effects of these mutations is needed. The fruit fly, Drosophila melanogaster, is an ideal model to study NDDs, with highly tractable genetics, combined with simple behavioral and circuit assays, permitting rapid medium-throughput screening of NDD/ID risk genes. Here, we review studies where the use of well-established assays to study mechanisms of learning and memory in Drosophila has permitted insights into molecular mechanisms underlying IDs. We discuss how technologies in the fly model, combined with a high degree of molecular and physiological conservation between flies and mammals, highlight the Drosophila system as an ideal model to study neurodevelopmental disorders, from genetics to behavior.
神经发育障碍（NDDs）包括许多病症，如脆性X综合征、自闭症谱系障碍和唐氏综合征等。它们的特征是适应性和社交行为受限，以及智力残疾（ID）。全外显子组和全基因组测序研究已凸显出大量的NDD/ID风险基因。为了剖析这些突变的遗传原因和潜在生物学途径，需要对这些突变的影响进行体内实验验证。果蝇（Drosophila melanogaster）是研究NDDs的理想模型，其遗传学易于操作，结合简单的行为和神经回路检测方法，能够对NDD/ID风险基因进行快速的中等通量筛选。在此，我们综述了一些研究，这些研究利用成熟的检测方法来研究果蝇的学习和记忆机制，从而深入了解ID背后的分子机制。我们讨论了果蝇模型中的技术，以及果蝇与哺乳动物之间高度的分子和生理保守性，如何凸显出果蝇系统是一个从遗传学到行为学研究神经发育障碍的理想模型。
