Kölsch Yvonne, Hahn Joshua, Sappington Anna, Stemmer Manuel, Fernandes António M, Helmbrecht Thomas O, Lele Shriya, Butrus Salwan, Laurell Eva, Arnold-Ammer Irene, Shekhar Karthik, Sanes Joshua R, Baier Herwig
Max Planck Institute of Neurobiology, Department Genes - Circuits - Behavior, 82152 Martinsried, Germany; Graduate School of Systemic Neurosciences, Ludwig Maximilian University, 82152 Martinsried, Germany.
Department of Chemical and Biomolecular Engineering, UC Berkeley, Berkeley, CA 94720, USA.
Neuron. 2021 Feb 17;109(4):645-662.e9. doi: 10.1016/j.neuron.2020.12.003. Epub 2020 Dec 23.
Retinal ganglion cells (RGCs) form an array of feature detectors, which convey visual information to central brain regions. Characterizing RGC diversity is required to understand the logic of the underlying functional segregation. Using single-cell transcriptomics, we systematically classified RGCs in adult and larval zebrafish, thereby identifying marker genes for >30 mature types and several developmental intermediates. We used this dataset to engineer transgenic driver lines, enabling specific experimental access to a subset of RGC types. Expression of one or few transcription factors often predicts dendrite morphologies and axonal projections to specific tectal layers and extratectal targets. In vivo calcium imaging revealed that molecularly defined RGCs exhibit specific functional tuning. Finally, chemogenetic ablation of eomesa RGCs, which comprise melanopsin-expressing types with projections to a small subset of central targets, selectively impaired phototaxis. Together, our study establishes a framework for systematically studying the functional architecture of the visual system.
视网膜神经节细胞（RGCs）构成了一系列特征检测器，将视觉信息传递到中枢脑区。为了理解潜在功能分离的逻辑，需要对RGC的多样性进行表征。利用单细胞转录组学，我们系统地对成年和幼体斑马鱼的RGC进行了分类，从而鉴定出30多种成熟类型和几种发育中间阶段的标记基因。我们利用这个数据集构建了转基因驱动系，从而能够对一部分RGC类型进行特定的实验研究。一种或少数转录因子的表达通常可预测树突形态以及向特定视顶盖层和视顶盖外靶点的轴突投射。体内钙成像显示，分子定义的RGC表现出特定的功能调谐。最后，对eomesa RGC进行化学遗传学消融，这些细胞包括表达黑视蛋白且投射到一小部分中枢靶点的类型，选择性地损害了趋光性。总之，我们的研究建立了一个系统研究视觉系统功能结构的框架。
