Cerebellar nuclei evolved by repeatedly duplicating a conserved cell type set

Abstract

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

Fruitless mutant male mosquitoes gain attraction to human odor

“…Another possibility is that mosquitoes duplicated and co-opted the ancestral fruitless-expressing mating neural circuits and retuned the inputs and outputs into this circuit to drive host-seeking. Circuit duplication is one of the mechanisms by which neural circuits are proposed to evolve (Tosches, 2017), and has been demonstrated in the case of vocal learning (Chakraborty and Jarvis, 2015) and in the evolution of cerebellar nuclei (Kebschull et al, 2020). In these duplicated mosquito circuits, fruitless function would have switched from promoting mating to inhibiting host-seeking in males.…”

Single-cell transcriptomes of developing and adult olfactory receptor neurons inDrosophila

“…Therefore, we established a single-nucleus RNA-seq (snRNA-seq) protocol to profile adult ORNs ( Figure 1C), as similar methods have been used to gain transcriptomic access to cell types that are resistant to standard dissociation protocols in other organisms (Habib et al, 2017;Denisenko et al, 2020;Ding et al, 2020;Kebschull et al, 2020). Our snRNA-seq protocol is comparable to our scRNA-seq method, in which GFP-labeled neurons in third antennal segment were dissected and dissociated into a single-cell suspension, sorted into 384-well plates via fluorescence activated cell sorting (FACS), and sequenced using the SMART-seq2 platform (Picelli et al, 2014) (Figure 1C, top).…”

“…Adult ORNs, like many insect tissues, are tightly associated with the hardened exoskeleton and are difficult to isolate using standard cell dissociation protocols. Nuclei, on the other hand, are much more resistant to mechanical assaults and have been readily profiled using snRNA-seq in multiple systems (Grindberg et al, 2013;Habib et al, 2016Habib et al, , 2017Cui et al, 2020;Kebschull et al, 2020;Lau et al, 2020). snRNA-seq has many advantages including: 1) tissue can be kept in long-term storage at -80ºC prior to extraction (Wu et al, 2019;Ding et al, 2020); 2) snRNAseq reduces cell-type sampling bias (Denisenko et al, 2020); and 3) nuclei are more easily captured by microfluidics devices than large and/or fragile cells (Cui et al, 2020;Denisenko et al, 2020).…”

Whole-animal connectome and cell-type complement of the three-segmentedPlatynereis dumeriliilarva

“…The cell-type diversification of mechanoreceptors may have been paralleled by the diversification of the postsynaptic INsplit neurons. The duplication and divergence of entire cell type sets has also been proposed for the evolution of the vertebrate cerebellum (Kebschull et al, 2020). Testing this model in Platynereis would require the integration of connectomics and comprehensive gene expression analysis.…”