Development/Plasticity/Repair Spatial Genetic Patterning of the Embryonic Neuroepithelium Generates GABAergic Interneuron Diversity in the Adult Cortex

Cortical pyramidal cells are generated from pallial neuroepithelial precursors, whereas GABAergic interneurons originate in subpallial germinal zones and migrate tangentially to reach the cortex. Using Cre–lox technology in transgenic mice and a series of molecular markers that subdivide the subpallial neuroepithelium into small domains, we fate-map precursor pools and identify interneurons generated fromeachdomain. Cortical interneurons expressing calbindin, parvalbumin, and somatostatin are generated exclusively from Lhx6 (Lim homeobox 6)-expressing precursors in the medial ganglionic eminence (MGE). Martinotti cells that coexpress calretinin and somatostatin are generated from the dorsal region of theMGE neuroepithelium that expressesNkx6.2 (NK2 transcription factor-related 6.2). Most neuropeptide Y-expressing cells and all bipolar calretinin-expressing interneurons are generated outside the MGE, from the germinal zones of the lateral/caudal ganglionic eminences that expressGsh2 (genomic screenedhomeobox 2). Our data demonstrate that subpallial neuroepithelial domains defined by expression of genetic determinants generate distinct interneuron subtypes, thereby con-tributing to the generation of cortical interneuron heterogeneity observed in the adult cortex. Key words: cell fate; cortex; Cre-transgenic; development; GABAergic neuron; interneuron