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

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 B Ding; Howard Y Chang; Karl Deisseroth; Stephen R Quake; Liqun Luo

doi:10.1126/science.abd5059

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

Science. 2020 Dec 18;370(6523):eabd5059. doi: 10.1126/science.abd5059.

Authors

Justus M Kebschull¹, Ethan B Richman^#^{1

2

3}, Noam Ringach^#¹, Drew Friedmann¹, Eddy Albarran², Sai Saroja Kolluru^{3

4

5}, Robert C Jones^{3

4}, William E Allen^{1

2

3

6}, Ying Wang⁷, Seung Woo Cho⁸, Huaijun Zhou⁷, Jun B Ding^{9

10}, Howard Y Chang^{8

11}, Karl Deisseroth^{3

11

12}, Stephen R Quake^{13

4

5}, Liqun Luo^{14

11}

Affiliations

¹ Department of Biology, Stanford University, Stanford, CA 94305, USA.
² Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
³ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
⁵ Chan Zuckerberg Biohub, Stanford, CA 94305, USA.
⁶ Society of Fellows, Harvard University, Cambridge, MA 02138, USA.
⁷ Department of Animal Science, University of California, Davis, CA 95616, USA.
⁸ Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
⁹ Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
¹⁰ Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
¹¹ Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
¹² Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
¹³ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. steve@quake-lab.org lluo@stanford.edu.
¹⁴ Department of Biology, Stanford University, Stanford, CA 94305, USA. steve@quake-lab.org lluo@stanford.edu.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biological Evolution*
Cerebellar Nuclei / cytology*
Cerebellar Nuclei / metabolism
Chickens
Female
Humans
Male
Mice
Mice, Inbred C57BL
Neurons / classification*
Neurons / metabolism
RNA-Seq

Abstract

Publication types

MeSH terms

Grants and funding