A combinatorial code of transcription factors specifies subtypes of visual motion-sensing neurons in Drosophila

Direction-selective T4/T5 neurons exist in four subtypes, each tuned to visual motion along one of the four cardinal directions. Along with their directional tuning, neurons of each T4/T5 subtype orient their dendrites and project their axons in a subtype-specific manner. Directional tuning, thus, appears strictly linked to morphology in T4/T5 neurons. How the four T4/T5 subtypes acquire their distinct morphologies development remains largely unknown. Here, we investigated when and how the dendrites of the four T4/T5 subtypes acquire their specific orientations, and profiled the transcriptomes of all T4/T5 neurons during this process. This revealed a simple and stable combinatorial code of transcription factors defining the four T4/T5 subtypes during their development. Changing the combination of transcription factors of specific T4/T5 subtypes resulted in predictable and complete conversions of subtype-specific properties, i.e. dendrite orientation and matching axon projection pattern. Therefore, a combinatorial code of transcription during factors coordinates the development of dendrite and axon morphologies to generate anatomical specializations differentiating subtypes of T4/T5 motion-sensing neurons. Overall design: Single-cell transcriptomic analysis of T4/T5 subtypes during different developmental stages

方向选择性T4/T5神经元存在四种亚型，每种亚型均针对四个基本方位之一的视觉运动产生调谐响应。伴随方向调谐特性，每种T4/T5亚型的神经元会以亚型特异性的方式排布树突并投射轴突。由此可见，T4/T5神经元的方向调谐特性与其形态结构严格相关。目前学界对四种T4/T5亚型如何在发育过程中获得各自独特的形态结构的机制仍知之甚少。本研究针对四种T4/T5亚型的树突如何以及何时获得其特异性取向展开探究，并对该过程中所有T4/T5神经元的转录组进行了分析表征。研究结果揭示了一套简洁且稳定的转录因子（transcription factors）组合编码，可在发育过程中定义四种T4/T5亚型。改变特定T4/T5亚型的转录因子组合，可使亚型特异性特征——即树突取向与匹配的轴突投射模式——发生可预测且完全的转换。因此，转录因子组合编码可协调树突与轴突形态的发育过程，进而产生区分T4/T5运动感知神经元亚型的解剖学特化结构。整体实验设计：针对不同发育阶段的T4/T5亚型开展单细胞转录组分析。