果蝇视觉系统中回路组装的转录程序。

Transcriptional Programs of Circuit Assembly in the Drosophila Visual System.

机构信息

Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Neuroscience Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Neuron. 2020 Dec 23;108(6):1045-1057.e6. doi: 10.1016/j.neuron.2020.10.006. Epub 2020 Oct 29.

DOI:10.1016/j.neuron.2020.10.006

PMID:33125872

Abstract

Precise patterns of synaptic connections between neurons are encoded in their genetic programs. Here, we use single-cell RNA sequencing to profile neuronal transcriptomes at multiple stages in the developing Drosophila visual system. We devise an efficient strategy for profiling neurons at multiple time points in a single pool, thereby minimizing batch effects and maximizing the reliability of time-course data. A transcriptional atlas spanning multiple stages is generated, including more than 150 distinct neuronal populations; of these, 88 are followed through synaptogenesis. This analysis reveals a common (pan-neuronal) program unfolding in highly coordinated fashion in all neurons, including genes encoding proteins comprising the core synaptic machinery and membrane excitability. This program is overlaid by cell-type-specific programs with diverse cell recognition molecules expressed in different combinations and at different times. We propose that a pan-neuronal program endows neurons with the competence to form synapses and that cell-type-specific programs control synaptic specificity.

摘要

神经元之间精确的突触连接模式被编码在它们的遗传程序中。在这里，我们使用单细胞 RNA 测序来描绘果蝇视觉系统发育过程中的多个阶段的神经元转录组。我们设计了一种在单个池中共检测多个时间点的有效策略，从而最大限度地减少批次效应并提高时间过程数据的可靠性。生成了一个跨越多个阶段的转录图谱，包括 150 多个不同的神经元群体；其中 88 个是通过突触发生追踪的。该分析揭示了一个共同的（全神经元）程序，在所有神经元中以高度协调的方式展开，包括编码构成核心突触机制和膜兴奋性的蛋白质的基因。该程序被具有不同组合和不同时间表达的不同细胞识别分子的细胞类型特异性程序所覆盖。我们提出，一个全神经元程序赋予神经元形成突触的能力，而细胞类型特异性程序控制突触特异性。