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.
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