Origin And Classification Of Cortical Interneurons In The Primate Brain

Cortical GABAergic inhibitory interneurons in mouse originate from subpallial progenitors and tangentially migrate to the cortex. While the majority of mouse cortical interneurons are derived from the medial and caudal ganglionic eminence (MGE and CGE, respectively), it remains unknown whether the lateral ganglionic eminence (LGE) also contributes to a subpopulation of cortical interneurons. We found that the transcription factor Sp8delineates dorsal lateral and dorsal caudal ganglionic eminence (dLGE and dCGE, respectively) in mouse embryonic forebrain. Sp8-expressing (Sp8+) cortical interneurons derived from dLGE/dCGE tangentially migrate mainly along the subventricular/intermediate zone (SVZ/IZ) route, and radially migrate from the SVZ/IZ into the cortical layers at later embryonic and early postnatal stages. Sp8+interneurons originate from dLGE/dCGE follow an outside-in layering pattern, preferentially occupying superficial cortical layers. The transcription factor Sp8is continuously expressed in mature cortical interneurons. In adult mouse cortex, we can classify vast majority of cortical interneurons using three transcription factors:Sox6, COUP-TFII and Sp8. According to combinatorial expression of transcription factors, we can study the origin of specific cortical interneuron subtypes. We systematically investigated the expression pattern of transcription factors that control cortical interneuron production in monkey and human embryonic forebrain. Although there are some differences, we found progenitor domains that producing cortical interneurons are conserved throughout the embryonic stages. In monkey and human embryonic forebrain, Sox6+cortical interneurons derived from MGE tangentially migrate into cortex through SVZ, SP/IZ and MZ. Expression of the transcription factor COUP-TFII in dLGE is easily observed. COUP-TFII+/Sp8+positive interneurons derived from dLGE/dCGE tangentially migrate along the subventricular/intermediate zone (SVZ/IZ) route at early embryonic stages and then along both SVZ/IZand marginal zone (MZ) at later embryonic stages. At postnatal0day (PO) monkey and full-term neonate cortex, there are still many COUP-TFII+/Sp8+cortical interneurons migration from SVZ. Transcription factors Sox6, COUP-TFII and Sp8are continuously expressed in adult monkey and human cortical interneurons. We classify cortical interneurons using three transcription factors in adult monkey and human cortex. We found PV+, SOM+, nNOS+, NPY+, CB and lightly-stained Reelin+cortical interneurons express Sox6, and originate from MGE. CR+, VIP+and densely-stained Reelin+cortical interneurons express COUP-TFII and Sp8, derived from dLGE/CGE. Our results demonstrate that the transcription factor Sp8specificlly labels dLGE/dCGE derived cortical interneurons from embryonic stages to adulthood in mouse and primates, and that the majority cortical interneurons of primate originate from the subpallium but not the pallium.