Mature interneuron subtypes arise from distinct spatial and temporal subdomains within the caudal ganglionic eminence

ABSTRACT Forebrain inhibitory interneurons are born from transient structures during embryogenesis known as the medial and caudal ganglionic eminences (MGE and CGE, respectively). The MGE and CGE generate distinct, non-overlapping cohorts of interneurons that can be defined by their transcriptomic, morphological, and electrophysiological characteristics. In the MGE, somatostatin-expressing (SST+) cells arise predominantly from the dorsal-posterior MGE from E12-E16 whereas parvalbumin-expressing (PV+) cells are born in the ventral-anterior MGE throughout embryogenesis. This relationship between spatiotemporal origin and mature interneuron subtypes has led to genetic insights regarding fate and maturation of these MGE-derived cells. A similar organization has never been explored in the CGE, despite the significant increase in CGE-derived interneurons in primates compared to rodents. Here we harvested fluorescent cells from distinct CGE subdomains at E13.5 and E15.5 and grafted them into WT neonatal mice cortices. One month post-transplantation, brains were immunostained for interneuron markers to relate mature CGE-derived interneurons with spatiotemporal origins within the CGE. Our results indicate that there are significant spatial biases in the CGE, with specific interneuron subtypes preferentially arising from distinct CGE subdomains. These biases are relatively stable over time, implying a minimal relationship between temporal birthdate and interneuron subtype. In the future, combining these insights with spatial transcriptome profiles will generate critical insights into gene regulation of CGE-derived interneurons.