Cerebellar nuclei evolved by repeatedly duplicating a conserved cell-type set

作者：Justus M. Kebschull, Ethan B. Richman, Noam Ringach, Drew Friedmann, Eddy Albarran, Sai Saroja Kolluru, Robert C. Jones, William E. Allen, Ying Wang, Seung Woo Cho, Huaijun Zhou, Jun Ding, Howard Y. Chang, Karl Deisseroth, Stephen R. Quake, Liqun Luo · 发表于：Science · 年份：2020 · DOI：10.1126/science.abd5059 · 被引用次数：259 · 研究领域：Single-cell and spatial transcriptomics、Neuroinflammation and Neurodegeneration Mechanisms、RNA Research and Splicing

How have complex brains evolved from simple circuits? Here we investigated brain region evolution at cell-type resolution in the cerebellar nuclei, the output structures of the cerebellum. Using single-nucleus RNA sequencing in mice, chickens, and humans, as well as STARmap spatial transcriptomic analysis and whole-central nervous system projection tracing, we identified a conserved cell-type set containing two region-specific excitatory neuron classes and three region-invariant inhibitory neuron classes. This set constitutes an archetypal cerebellar nucleus that was repeatedly duplicated to form new regions. The excitatory cell class that preferentially funnels information to lateral frontal cortices in mice becomes predominant in the massively expanded human lateral nucleus. Our data suggest a model of brain region evolution by duplication and divergence of entire cell-type sets.