Reconstructing the ancestral vertebrate brain using a lamprey neural cell type atlas

The vertebrate brain emerged more than ~500 million years ago in common evolutionary ancestors. To systematically trace its cellular and molecular origins, we established a spatially resolved cell type atlas of the entire brain of the sea lamprey - a jawless species whose phylogenetic position affords the reconstruction of ancestral vertebrate traits - based on extensive single-cell RNA-seq and in situ sequencing data. Comparisons of this atlas to neural data from the mouse and other jawed vertebrates unveiled various shared features that enabled the reconstruction of the core cell type composition, tissue structures, and gene expression programs of the ancestral brain. However, our analyses also revealed key tissues and cell types that arose later in evolution. For example, the ancestral vertebrate brain was likely devoid of cerebellar cell types and oligodendrocytes (myelinating cells); our data suggest that the latter emerged from astrocyte-like evolutionary precursors on the jawed vertebrate lineage. Our work illuminates the cellular and molecular architecture of the ancestral vertebrate brain and provides a foundation for exploring its diversification during evolution. ; The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. We thank all members of the Kaessmann group for the fruitful discussions; Elisa Panzariello, Marta Sanchez-Delgado, Nils Trost for the brain and animal illustrations, Moritz Mall for providing temporary lab-space and assistance, and Margarida Cardoso-Moreira for discussions and comments on the manuscript. Computations were performed on the Kaessmann lab server (managed by Nils Trost) and the bwForCluster from the Heidelberg University Computational Center (supported by the state of Baden-Württemberg through bwHPC and the German Research Foundation – INST 35/1134-1 FUGG). This research was supported by grants from the European Research ...