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

• Published in: Science (American Association for the Advancement of Science) Vol. 370; no. 6523
• Main Authors: Kebschull, Justus M., Richman, Ethan B., Ringach, Noam, Friedmann, Drew, Albarran, Eddy, Kolluru, Sai Saroja, Jones, Robert C., Allen, William E., Wang, Ying, Cho, Seung Woo, Zhou, Huaijun, Ding, Jun B., Chang, Howard Y., Deisseroth, Karl, Quake, Stephen R., Luo, Liqun
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 18.12.2020
• Subjects: Amphibians; Anatomy; Animals; Biological Evolution; Brain; Brain architecture; Brain mapping; Cell culture; Central nervous system; Cerebellar Nuclei - cytology; Cerebellar Nuclei - metabolism; Cerebellum; Chickens; Circuits; Cognitive ability; Cognitive Processes; Cortex (frontal); Divergence; Duplication; Evolution; Feedforward control; Female; Funnels; Gene expression; Gene sequencing; Hindbrain; Humans; Invariants; Male; Mapping; Mice; Mice, Inbred C57BL; Motor task performance; Neurons; Neurons - classification; Neurons - metabolism; Nuclei (cytology); Poultry; Projection; Reproduction (copying); Reprography; Reptiles; Ribonucleic acid; RNA; RNA-Seq; Spatial analysis; Spinal cord; Substructures; Thalamic nuclei; Thalamus; Tracing; Transcription; Transcriptomics; Vertebrates
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abd5059

Cerebellar nuclei, substructures of the cerebellum, transfer information from the cerebellum to other parts of the brain. Using single-cell transcriptomics, Kebschull et al. have now identified a conserved pattern of cerebellar nuclei structure that has been repeated through evolution (see the Perspective by Hatten). Ranging from mice to chickens to humans, cerebellar nuclei are made up of region-specific excitatory neurons and region-invariant inhibitory neurons. In humans, a facet connecting the cerebellum to the frontal cortex is enhanced. Science , this issue p. eabd5059 ; see also p. 1411 Evolutionary duplication and divergence of a conserved cell type set account for the expansion of the brain’s cerebellar nuclei. 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.