Abstract

The number and diversity of inhibitory neurons (INs) increased substantially during mammalian brain evolution. However, the generative mechanisms of the vast repertoire of human INs remain elusive. We performed spatial and single-cell transcriptomics of human medial ganglionic eminence (hMGE), a pivotal source of cortical and subpallial INs, and built the trajectories of hMGE-derived cells during brain development. We identified spatiotemporally and molecularly segregated progenitor cell populations fated to produce distinct IN types. We uncovered an evolutionarily distinct progenitor cell type in the hMGE subventricular zone that maintained the production of INs and glial cells throughout human brain development. Our findings reveal evolutionarily distinct features of IN generation and shed light on the distinct mechanisms underlying human brain development.