Periodic Reporting for period 2 - VerteBrain (The ancestral vertebrate brain and its cellular diversification during evolution)
Berichtszeitraum: 2023-07-01 bis 2024-12-31
The question of how new organs originate and evolve is fundamental to understanding the evolution of complex animals.
Recent single-cell genomics technologies permit detailed investigations of the evolutionary "birth" of organs and constituent cell types. Here, we will scrutinize the origins and cellular evolution of the vertebrate brain by generating and analyzing extensive single-cell transcriptomic, epigenomic, and spatial transcriptomic data across species representing all major vertebrate lineages.
The project has three interlaced aims: In Aim 1, we will infer the cell type repertoire of the ancestral vertebrate brain and its regulatory and molecular foundations, by comparing single-cell data across the most diverged vertebrate species. In Aim 2, we will trace the cell type diversification of the ancestral brain during evolution and underlying regulatory and molecular changes. We will first investigate the origination of two key cell types (oligodendrocytes and Purkinje cells) that underlie the emergence of neuron insulation and the cerebellum, respectively, thus facilitating functional elaborations of the jawed vertebrate brain. We will then compare rates of cellular evolution across brain structures and test the hypothesis that cell type innovation was most frequent in the pallium, which affords advanced cognitive functions and experienced massive structural changes during evolution. In Aim 3, we will focus on the amniote pallium, a preeminent model for understanding neural tissue diversification. We will scrutinize the origins, development, and evolutionary relationships of cell types in three new structures: neocortex, dorsal ventricular ridge, and Wulst. Two of these structures – the neocortex in mammals and Wulst in birds – facilitated the convergent evolution of advanced cognitive abilities.
Overall, our work will provide an overview of the cellular evolution of the vertebrate brain and, more generally, illuminate principles of cell type evolution.
Recent single-cell genomics technologies permit detailed investigations of the evolutionary "birth" of organs and constituent cell types. Here, we will scrutinize the origins and cellular evolution of the vertebrate brain by generating and analyzing extensive single-cell transcriptomic, epigenomic, and spatial transcriptomic data across species representing all major vertebrate lineages.
The project has three interlaced aims: In Aim 1, we will infer the cell type repertoire of the ancestral vertebrate brain and its regulatory and molecular foundations, by comparing single-cell data across the most diverged vertebrate species. In Aim 2, we will trace the cell type diversification of the ancestral brain during evolution and underlying regulatory and molecular changes. We will first investigate the origination of two key cell types (oligodendrocytes and Purkinje cells) that underlie the emergence of neuron insulation and the cerebellum, respectively, thus facilitating functional elaborations of the jawed vertebrate brain. We will then compare rates of cellular evolution across brain structures and test the hypothesis that cell type innovation was most frequent in the pallium, which affords advanced cognitive functions and experienced massive structural changes during evolution. In Aim 3, we will focus on the amniote pallium, a preeminent model for understanding neural tissue diversification. We will scrutinize the origins, development, and evolutionary relationships of cell types in three new structures: neocortex, dorsal ventricular ridge, and Wulst. Two of these structures – the neocortex in mammals and Wulst in birds – facilitated the convergent evolution of advanced cognitive abilities.
Overall, our work will provide an overview of the cellular evolution of the vertebrate brain and, more generally, illuminate principles of cell type evolution.
The vertebrate brain emerged more than ~500 million years ago in common evolutionary ancestors. To systematically trace its cellular and molecular origins, we completed during the first reporting period our project's pilot project, in which 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 cell types, tissue structures and gene expression programs of the ancestral vertebrate brain. However, our analyses also revealed key tissues and cell types that arose later in evolution. For example, the ancestral brain was probably devoid of cerebellar cell types and oligodendrocytes (myelinating cells); our data suggest that the latter emerged from astrocyte-like evolutionary precursors in the jawed vertebrate lineage. Altogether, this major initial work in the framework of our "VerteBrain" ERC endeavor illuminates the cellular and molecular architecture of the ancestral vertebrate brain and provides a foundation for exploring its diversification during evolution.
The aforementioned work was already recently published in the journal Nature Ecology and Evolution (https://www.nature.com/articles/s41559-023-02170-1(öffnet in neuem Fenster)).
Comparisons of this atlas to neural data from the mouse and other jawed vertebrates unveiled various shared features that enabled the reconstruction of cell types, tissue structures and gene expression programs of the ancestral vertebrate brain. However, our analyses also revealed key tissues and cell types that arose later in evolution. For example, the ancestral brain was probably devoid of cerebellar cell types and oligodendrocytes (myelinating cells); our data suggest that the latter emerged from astrocyte-like evolutionary precursors in the jawed vertebrate lineage. Altogether, this major initial work in the framework of our "VerteBrain" ERC endeavor illuminates the cellular and molecular architecture of the ancestral vertebrate brain and provides a foundation for exploring its diversification during evolution.
The aforementioned work was already recently published in the journal Nature Ecology and Evolution (https://www.nature.com/articles/s41559-023-02170-1(öffnet in neuem Fenster)).
Overall, based in the generation and cross-vertebrate analyses of cell type atlases and underlying gene expression/gene regulatory (i.e. snRNA-seq and snATAC-seq data) our work will provide a major overview of the cellular evolution of the vertebrate brain and, more generally, illuminate principles of cell type evolution.