Conférence - Arnold Kriegstein: The Origin of Cortical Interneurons in Human Brain Development

Jean-Jacques Hublin Chaire Paléoanthropologie Collège de France Année 2026-2027

Insights into the Development, Evolution, and Diseases of the Human Neocortex Conférence - Arnold Kriegstein: The Origin of Cortical Interneurons in Human Brain Development

Arnold Kriegstein Professeur de neurologie, université de Californie, San Francisco

Résumé

Evolutionary expansion of the human forebrain required increased production of inhibitory, GABAergic neurons by the ganglionic eminences, yet the mechanisms remain unclear. Using multiome sequencing, spatial transcriptomics, live imaging, electron microscopy and organoid models, we identify diverse progenitors including outer radial glia-like cells. The primate medial ganglionic eminence exhibits distinctive cytoarchitecture with progenitors surrounding interconnected doublecortin-enriched nests (DENs) including newborn neurons. A PCDH19-dependent adhesion code contributes to DENs formation, while progenitor-restricted PCDH19 expression tracks with the presence of DENs across species. Thus, expanded progenitor diversity and specialized tissue architecture represent coordinated developmental innovations supporting increased inhibitory neuron production in primates.