Cell-type profiling in salamanders identifies innovations in vertebrate forebrain evolution

Abstract

The evolution of advanced cognition in vertebrates is associated with two independent innovations in the forebrain: the six-layered neocortex in mammals and the dorsal ventricular ridge (DVR) in sauropsids (reptiles and birds). How these innovations arose in vertebrate ancestors remains unclear. To reconstruct forebrain evolution in tetrapods, we built a cell-type atlas of the telencephalon of the salamander Pleurodeles waltl . Our molecular, developmental, and connectivity data indicate that parts of the sauropsid DVR trace back to tetrapod ancestors. By contrast, the salamander dorsal pallium is devoid of cellular and molecular characteristics of the mammalian neocortex yet shares similarities with the entorhinal cortex and subiculum. Our findings chart the series of innovations that resulted in the emergence of the mammalian six-layered neocortex and the sauropsid DVR.

Benchmarking strategies for cross-species integration of single-cell RNA sequencing data

“…Moreover, expression similarity of cells cross-species may arise from several reasons including homology, convergence and concerted evolution 8 . It is important to disentangle the source of the shared expression features to achieve deeper understanding of cell types 10 . Finally, one-to-one homologous relationship between cell types might not hold for evolutionarily distant species, as cell types have undergone complex evolution of identity-defining gene networks (see the interconnected cell type groups across Metazoa demonstrated in the SAMap study 23 ).…”

“…Recently, single-cell RNA-sequencing (scRNA-seq) and single-nucleus RNA-sequencing (snRNA-seq) have been applied in a diversity of species, generating full-scale cell atlases from transcriptome profiles of millions of individual cells 1–7 . Comparing cellular expression profiles cross-species provides insights into the origin and evolution of organs and cell types 6,8–10 , highlights species-specific transcriptomic innovations 11 , as well as further delineates how cell types execute their functions in health and disease 12,13 .…”

A marmoset brain cell census reveals influence of developmental origin and functional class on neuronal identity

“…Within telencephalic structures, there is strong partitioning of glutamatergic and GABAergic neurons in mammals as well as in amphibians ( 20 ), suggesting an evolutionarily conserved distinction. In mouse, glutamatergic and GABAergic neurons from diencephalic and midbrain structures also partition almost perfectly by neurotransmitter usage ( 7 ).…”

“…Glutamatergic neurons sampled from distinct cortical locations have regionally distinct gene expression ( 14 ), and primate cortical GABAergic interneurons also harbor regional gene expression differences ( 3 ). Glial types – particularly astrocytes – are heterogenous across the major cephalic subdivisions in mouse ( 2 , 7 , 20 , 21 ) and primate brain ( 4 ); but the extent to which they are locally customized in distinct regions of neocortex is less well understood. Transcriptomic profiling in the mouse has revealed layer-specific astrocyte subpopulations in the cortex ( 22 ) and heterogeneity within cortical and hippocampal astrocytes ( 23 ), but these studies did not systematically compare astrocyte transcriptomes within distinct cortical subregions.…”

“…In the vertebrate central nervous system, glutamate is the primary excitatory neurotransmitter, while GABA or glycine are inhibitory. Within the neocortex and other telencephalic structures, transcriptomically-defined neuron types hierarchically group first into GABAergic types and glutamatergic types ( 2 , 7 , 20 ), a distinction that reflects these types’ distinct developmental origins. In the mouse, other structures such as those found in the diencephalon and mesencephalon similarly segregate initially by GABAergic and glutamatergic status ( 7 ).…”