Molecular architecture of primate specific neural circuit formation

Abstract The mammalian cortex is a highly evolved brain region, but we still lack a comprehensive understanding of the molecular mechanisms underlying primate-specific neural circuits formation. In this study, we employed spatial transcriptomics to assess gene expression dynamics in the marmoset cortex during development, focusing on key regions and time points. Spatial transcriptomics identified genes that are sexually, spatially, and temporally differentially expressed in the developing marmoset cortex. Our detailed analysis of the visual cortex unveiled dynamic changes in gene expression across layers with distinct projections and functions. Notably, we discovered numerous axon guidance molecules with spatiotemporal expression patterns unique to the developing marmoset prefrontal cortex (PFC), which control PFC neuronal circuits. Among these molecules, PRSS12 (Protease, Serine, 12 (neurotrypsin, motopsin), when ectopically expressed in the mouse prelimbic cortex, caused similar changes in connectivity as observed in the marmoset A32 area. Furthermore, PRSS12 showed similar expression patterns in both marmoset and human PFC during development, suggesting parallels between marmoset and human brain development. The differential expression of axon guidance molecules in the developing PFC, varying by region, likely contributes to the formation of unique circuits observed in primates.