Nuclear receptor COUP-TFII-expressing neocortical interneurons are derived from the medial and lateral/caudal ganglionic eminence and define specific subsets of mature interneurons.

Neocortical GABAergic interneurons in rodents originate from subpallial progenitor zones. The majority of mouse neocortical interneurons are derived from the medial and caudal ganglionic eminences (MGE and CGE, respectively) and the preoptic area (POA). It is controversial whether the lateral ganglionic eminence (LGE) also generates neocortical interneurons. Previously it was shown that the transcription factor COUP-TFII is expressed in the CGE; here we show that COUP-TFII is also expressed in the dorsal MGE, dorsal LGE (dMGE and dLGE, respectively), and POA. In the adult neocortex, COUP-TFII+/somatostatin (SOM)+ interneurons are mainly located in layer V. Using a genetic fate-mapping approach (Shh-Cre and Nkx2.1-Cre), we demonstrate that the POA and ventral MGE do not give rise to COUP-TFII+ neocortical interneurons, suggesting that the dMGE is the source of COUP-TFII+/SOM+ neocortical interneurons. We also observed a migratory stream of COUP-TFII+/Sp8+ cells emanating from the dLGE and CGE to the neocortex mainly through the subventricular zone at later embryonic stages. Slice culture experiments in which dLGE progenitors were labeled with BrdU provided additional evidence that the dLGE generates neocortical interneurons. While earlier-born dMGE-derived COUP-TFII+ interneurons occupy cortical layer V, later-born dLGE- and CGE-derived COUP-TFII+ ones preferentially occupy superficial cortical layers. A similar laminar distribution was observed following neonatal transplantation of embryonic day (E)14.5 dMGE and E15.5 dLGE. These results provide novel information about interneuron fate and position from spatially and temporally distinct origins in the ganglionic eminences.