Chen Dahong, Dale Ryan K, Lei Elissa P
Nuclear Organization and Gene Expression Section, Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Nuclear Organization and Gene Expression Section, Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Development. 2018 Jan 3;145(1):dev154047. doi: 10.1242/dev.154047.
Neuronal remodeling is crucial for formation of the mature nervous system and disruption of this process can lead to neuropsychiatric diseases. Global gene expression changes in neurons during remodeling as well as the factors that regulate these changes remain poorly defined. To elucidate this process, we performed RNA-seq on isolated larval and pupal neurons and found upregulated synaptic signaling and downregulated gene expression regulators as a result of normal neuronal metamorphosis. We further tested the role of (), which encodes an evolutionarily conserved RNA-binding protein required for proper neuronal remodeling. Depletion of in neurons prevents the execution of metamorphic gene expression patterns, and regulated genes correspond to Shep chromatin and/or RNA-binding targets. Reduced expression of a Shep-inhibited target gene that we identified, , is sufficient to rescue neuronal remodeling defects of knockdown flies. Our results reveal direct regulation of transcriptional programs by Shep to regulate neuronal remodeling during metamorphosis.
神经元重塑对于成熟神经系统的形成至关重要，而这一过程的破坏会导致神经精神疾病。在重塑过程中神经元的全局基因表达变化以及调节这些变化的因素仍不清楚。为了阐明这一过程，我们对分离出的幼虫和蛹神经元进行了RNA测序，发现正常神经元变态导致突触信号上调和基因表达调节因子下调。我们进一步测试了（）的作用，它编码一种神经元正常重塑所需的进化保守RNA结合蛋白。神经元中（）的缺失会阻止变态基因表达模式的执行，且受调控的基因对应于Shep染色质和/或RNA结合靶点。我们鉴定出的一个受Shep抑制的靶基因（）的表达降低，足以挽救敲低（）的果蝇的神经元重塑缺陷。我们的结果揭示了Shep对转录程序的直接调控，以在变态过程中调节神经元重塑。
