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

Abstract

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.

linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells

“…4c, dashed box). These data indicate that linc-mipep and linc-wrb preferentially regulate oligodendrocyte and cerebellar cell states during development – evolutionarily newer vertebrate brain cell types 27 .…”

“…This ancestral protein is likely derived from an unannotated ORF in the invertebrate Amphioxus (lancelet) encoding for an APEX1-like gene in the HMGN1 syntenic region. Neural crest cells, myelinating cells (both oligodendrocytes in the CNS and neural crest-derived Schwann cells in the peripheral nervous system), and cerebellar cells (including granule cells) are considered to be among these jawed vertebrate-specific innovations 27,34 . We hypothesize that linc-mipep, linc-wrb, and HMGN1 co-evolved with the gene regulatory networks that establish these cell types in development, in line with previous findings [35][36][37][38][39][40] , as we find that these evolutionarily newer brain cell types are most affected by loss of linc-mipep and linc-wrb in zebrafish.…”

Direct and indirect neurogenesis generate a mosaic of distinct glutamatergic projection neuron types in cerebral cortex

“…Indeed, recent studies suggest that extant amniotes possess a variety of divergent pallial structures, from six-layered neocortex in mammals to three-layered dorsal cortex in non-avian reptiles to nucleus-like pallia in birds. They share a conserved set of neuronal cell types and circuitries, the basic elements of which can be traced back even to the earliest of vertebrates (Briscoe and Ragsdale, 2018; Cardenas and Borrell, 2020; Lamanna et al, 2022; Suryanarayana et al, 2021) (Fig 5). A key approach in this cell type perspective of cortical evolution is to delineate the developmental trajectories from progenitor types to neuronal cell types in the assembly of brain circuits.…”

Organization of the corticotropin‐releasing hormone and corticotropin‐releasing hormone‐binding protein systems in the central nervous system of the sea lamprey Petromyzon marinus

“…However, correspondence with lamprey hindbrain PmCRH‐expressing populations is unclear. Moreover, the sea lamprey lacks catecholaminergic populations in the rostral rhombencephalon and does not have a locus coeruleus homologue (Barreiro‐Iglesias, Laramore, et al., 2010 ), and lacks an inferior olivary nucleus, whose CRHergic cells project to the cerebellum in mammals (which is also absent in lampreys; see Lamanna et al., 2022 ).…”

“…Lampreys are interesting for comparative studies due to the position they occupy in the vertebrate phylogeny, the lamprey lineage together with myxines (hagfishes) belongs to the agnatha, the sister out‐group of gnathostomes (Delarbre et al., 2002 ; Forey & Janvier, 1993 ; Furlong & Holland, 2002 ; Kuratani & Ota, 2008 ; Murakami et al., 2005 ). The brain of lampreys exhibits the basic cell types, regions, and structures of the vertebrate brain (Lamanna et al., 2022 ; Murakami & Kuratani, 2008 ). Research on the nervous, endocrine, and immune systems of lampreys has significance for revealing the origin and evolution of these systems, to infer the ancestral organization of the brain in vertebrates and could also contribute to a better understanding of human diseases and treatments (see Barreiro‐Iglesias & Rodicio, 2012 ; Sobrido‐Cameán & Barreiro‐Iglesias, 2022 ).…”