Cerebellar nuclei evolved by repeatedly duplicating a conserved cell-type set.
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.
1. Exploring tissue architecture using spatial transcriptomics.
2. Systematizing and cloning of genes involved in the cerebellar cortex circuit development.
3. Spatial and cell type transcriptional landscape of human cerebellar development.
4. Three-dimensional intact-tissue sequencing of single-cell transcriptional states.
5. scGRNom: a computational pipeline of integrative multi-omics analyses for predicting cell-type disease genes and regulatory networks.
1. Molecular specification of cell types underlying central and peripheral vision in primates
2. Molecular specification of cell types underlying central and peripheral vision in primates (macaque fovea single cell RNA-seq)
3. Molecular specification of cell types underlying central and peripheral vision in primates (macaque peripheral single cell RNA-seq)
4. Dissecting cell-type composition and activity-dependent transcriptional state in mammalian brains by massively parallel single-nucleus RNA-Seq