Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex

Abstract

Callosal projection neurons (CPN) interconnect the neocortical hemispheres via the corpus callosum, and are implicated in associative integration of multi-modal information. CPN have undergone differential evolutionary elaboration, leading to increased diversity of cortical neurons – and more extensive and varied connections in neocortical gray and white matter – in primates compared to rodents. In mouse, distinct sets of genes are enriched in discrete subpopulations of CPN, indicating the molecular diversity of rodent CPN. Elements of rodent CPN functional and organizational diversity might thus be present in the further elaborated primate cortex. We address the hypothesis that genes controlling mouse CPN subtype diversity might reflect molecular patterns shared among mammals that arose prior to the divergence of rodents and primates. We find that, while early expression of the examined CPN-enriched genes, and post-migratory expression of these CPN-enriched genes in deep layers are highly conserved (e.g. Ptn, Nnmt, Cited2, Dkk3), by contrast, the examined genes expressed by superficial layer CPN show more variable levels of conservation (e.g. EphA3, Chn2). These results suggest that there has been evolutionarily differential retraction and elaboration of superficial layer CPN subpopulations between mouse and macaque, with independent derivation of novel populations in primates. Together, these data inform future studies regarding CPN subpopulations that are unique to primates and rodents, and indicate putative evolutionary relationships.