Single-cell transcriptomics reveals evolutionary innovations in reptile and amphibian brains

Across four studies, evolutionary innovations in reptile and amphibian brains are revealed via comparative single-cell transcriptomics. While vertebrate brain evolution traditionally has focused on similarities in brain regions across disparate species, this new research highlights the role of cell type evolution in vertebrate brain innovations. Over the past several years, hundreds of distinctive cell types have been identified in specialized brain regions in mice. However, how such a diversity of cell types and regions evolved remains unknown. Here, in four studies, researchers use single-cell and spatial transcriptomics to investigate cell type evolution at the brain scale in reptiles and amphibians to understand this diversity’s evolutionary roots better.

In the first study, David Hain and colleagues used single-cell transcriptomics to create a whole-brain cell atlas of the bearded dragon lizard and compared it to that of the mouse. Hain et al. found that cells from broadly defined brain regions in both species correspond to each other, suggesting deeply conserved region-specific gene expression signatures. However, when mapped at a higher resolution, the authors observed very dissimilar cell types across species in nearly every brain division. The existence of conserved and new cell types within conserved brain regions indicates that brain cell types are evolutionarily plastic and capable of independently evolving new and innovative expression signatures and functions.

Three other studies expand upon these findings, focusing on the amphibian’s telencephalon – the part of the brain that in mammals contains the six-layered neocortex, which amphibians lack. Jamie Woych and colleagues assembled a cell-type atlas of this region to chart the evolutionary innovations that set it apart from other vertebrate brains. Katharina Lust and colleagues and Xiaoyu Wei and colleagues present single-cell analyses of the axolotl telencephalon, with particular attention paid to understanding why this animal’s brain is so much more capable of regeneration than the mammalian brain. “These studies highlight the potential of applying the powerful transcriptomic methods that are usually reserved for mouse to nonstandard models,” write Dylan Faltine-Gonzalez and Justus Kebschull in a related Perspective. “Each of the articles produced massive single-cell and often multimodal datasets and mined publicly available data, showcasing the importance of data sharing and the power of accumulating single-cell data from many species for evolutionary comparisons.”