Linking developmental trajectories to neural circuit function in the Drosophila visual motion detection system

为了形成服务于行为的脑回路，神经元导航从神经祖细胞到功能模式特异性回路的发育轨迹。这种发育轨迹如何赋予神经元身份和功能特性是一个未解决的与健康和疾病相关的问题。我们使用果蝇视觉运动敏感系统来研究这个问题。方向选择性运动敏感的T4/T5神经元是一个强大的模型，可以理解(1)如何实现方向选择性以调整T4/T5神经元到四个基本方向，(2)如何指定相应的神经元亚型。我们实验室的研究结果表明，有必要重新审视当前的范式，将只有四种功能性T4/T5亚型的规范与预定数量的祖细胞分裂联系起来：Hassan实验室证明了短暂的祖细胞扩增，可能导致比预期更多的T4/T5细胞，Silies实验室表明有六种功能性亚型编码光流模式。总之，我们的发现表明，瞬时扩增随后是功能专门化和神经元消除，为与行为相关的六种功能类型提供了发展基础。我们将验证这一假设，并阐明发育如何产生具有功能特性的神经元。我们的专业知识的结合将揭示刻板的T4/T5细胞数量和功能特化如何从一个可变的起始祖细胞群体中建立的时间轨迹。对投射到4个解剖层的6个亚型的功能分析，对上游和下游光流神经元的T4/T5连接模式进行了具体预测，这将利用果蝇遗传工具和连接组学的独特组合进行探索。我们的工作将阐明发育机制在多大程度上指导功能性神经回路特性，最终为动物行为服务。

To form brain circuits that serve behavior, neurons navigate a developmental trajectory from neural progenitors to functional modality-specific circuits. How this developmental trajectory endows neurons with identity and functional properties is an unsolved problem of relevance to health and disease. We use the Drosophila visual-motion sensitive system to investigate this question. The direction-selective motion-sensitive T4/T5 neurons are a powerful model to understand (1) how direction selectivity is achieved to tune T4/T5 neurons to four cardinal directions and (2) how the corresponding neuronal subtypes are specified. Findings from our labs suggest a need to revisit the current paradigm linking the specification of only four functional T4/T5 subtypes to a predetermined number of progenitor divisions: The Hassan lab demonstrated transient progenitor amplification, potentially leading to more T4/T5 cells than expected, and the Silies lab showed that there are six functional subtypes encoding optic flow patterns. Together, our discoveries suggest that transient amplification followed by functional specialization and neuronal elimination provide a developmental basis for the six functional types relevant for behavior. We will test this hypothesis and elucidate how development generates neurons with functional properties. Our combination of expertise will unravel the temporal trajectory of how the stereotyped T4/T5 cell number and functional specialization is established from a variable starting population of progenitors. Functional analysis of six subtypes projecting to four anatomical layers makes specific predictions about T4/T5 connectivity patterns to upstream and downstream optic flow neurons that will be explored using a unique combination of genetic tools and connectomics available in Drosophila. Our work will elucidate to what extent developmental mechanisms instruct functional neural circuit properties ultimately tuned to serve animal behavior.