A comparative brain cell atlas of Astyanax mexicanus

After establishing the molecular signatures of 35 cell types, we show that cave colonization drove canalized regulatory changes to gene expression that persist in the laboratory environment. Cavefish brains show shifts in cell type composition compared to their surface counterparts, as well as complex regulatory changes to pathways governing hypoxia response and circadian rhythm. Microglia in the cavefish brain underwent extensive transcriptional remodelling, including changes in senescence and AMPK pathways.

Further, cell-cell communication analysis identified a cave-enriched ligand-receptor communication pattern centered on signals sent from glial cells to diverse populations of neurons. This atlas highlights discoveries on how brains adapt to new environments and provides a resource for future studies of brain evolution in A. mexicanus, an emerging model for translational research into neurodegenerative disease in humans.