Comparative transcriptomics reveals differences in cortical cell type organization between metatherian and eutherian...

Area of Science:

• Neuroscience
• Comparative Biology
• Genomics

Background:

• The mammalian neocortex, crucial for higher cognitive functions, possesses a conserved laminar architecture.
• However, the cell-type specific organization within cortical columns across diverse mammalian lineages remains poorly understood.

Purpose of the Study:

• To compare the gene expression, cell types, and laminar organization of the primary visual cortex (V1) between a metatherian (Monodelphis domestica) and a eutherian (Mus musculus) mammal.
• To investigate evolutionary variations in cortical column structure.

Main Methods:

• Single-nucleus RNA sequencing (snRNA-seq) was employed to analyze gene expression at the cellular level.
• Spatial transcriptomics provided insights into the spatial organization of cell types within the V1.

Main Results:

• Significant differences in spatio-transcriptomic distinctions were observed between supragranular (layer 2/3) and infragranular (layer 5) intratelencephalic neurons in mice compared to Monodelphis.
• The mouse cortex showed a lower relative density of parvalbumin-positive GABAergic neurons and altered perineuronal net distribution.
• These findings suggest lineage-specific specializations and altered plasticity constraints in the mouse neocortex.

Conclusions:

• The cellular and spatial organization of the cortical column exhibits substantial variation across deeply diverged mammalian species.
• This challenges the long-held assumption of uniform conservation in local cortical architecture.
• Evolutionary divergence significantly impacts neocortical organization and function.