Multimodal analysis of neuronal maturation in the developing primate prefrontal cortex.

The dorsolateral prefrontal cortex (dlPFC) is a derived cortical area in primates that is involved in myriad high-cognitive functions and is associated with several neuropsychiatric disorders. Here, we performed Patch-seq and single-nucleus multiomic analyses of the rhesus macaque dlPFC to identify genes governing neuronal maturation during midfetal to late-fetal development. Our multimodal analyses have identified genes and pathways important for the maturation of distinct neuronal populations as well as genes underlying the maturation of specific electrophysiological properties. Using gene knockdown in macaque and human organotypic slices, we functionally tested the role of RAPGEF4 , a gene involved in synaptic remodeling, and CHD8 , a high-confidence autism spectrum disorder risk gene, on the electrophysiological and morphological maturation of excitatory neurons in the macaque and human fetal dlPFC.