Converging evidence indicates that the MGE is the origin of ∼50–60% of the population of cortical interneurons in the mouse. In particular, the MGE gives rise to the

large majority of PV-containing and SST-containing interneurons (Fig. 3). This later group is rather heterogeneous, including cells that also contain reelin, NPY and/or CR and have distinct electrophysiological properties and morphologies (Xu et al., 2006; Miyoshi et al., 2010). Both PV- and SST-containing interneurons greatly depend on Nkx2-1 for their normal generation. The analysis of Nkx2-1 mutants selleck screening library has already revealed that this transcription factor is required for the generation of more than half of the GABAergic cells populating the cortex (Sussel et al., 1999), but it has only become clear recently that this correspond to these specific classes of interneurons. Thus, both in vitro experiments (Xu et al., 2004; Wonders et al., 2008) and in vivo transplantation analyses (Wichterle et al., 2001; Butt et al., 2005; Cobos et al., 2005; Flames et al., 2007; Wonders et al., 2008) have revealed that the majority of cortical interneurons derived from the MGE are PV-containing

(∼65%) while the remaining cells (∼35%) express SST. These studies have recently been confirmed by genetic fate-mapping studies that took advantage of the existence of genes with patterns of expression that are largely confined to the MGE, such as Nkx2-1 and Lhx6 (Fogarty et al., 2007; Xu et al., 2008), as well as by the analysis of

null or conditional mutants for these genes (Liodis Bcl-xL protein Cell press et al., 2007; Butt et al., 2008; Zhao et al., 2008). A question that remains open is to what extent progenitor cells that give rise to PV- and SST-containing interneurons are spatially segregated within the MGE. The analysis of the expression pattern of several dozens of transcription factors within the ventricular zone of the MGE has led to the proposal that this region may consist of up to five distinct progenitor domains, designated pMGE1 to pMGE5, which it has been hypothesized give rise to different classes of neurons (Flames et al., 2007). Consistently, several lines of evidence suggest that the dorsal (pMGE1-2) and ventral (pMGE3-5) regions of the MGE have a tendency to preferentially give rise to SST- and PV-containing interneurons, respectively (Flames et al., 2007; Fogarty et al., 2007; Wonders et al., 2008). Furthermore, recent fate-mapping analyses have suggested that the progenitor cells giving rise to PV-containing GABAergic neurons populating the basal ganglia might also be spatially segregated from those producing PV-containing GABAergic interneurons for the cortex (Nóbrega-Pereira et al., 2008; Flandin et al., 2010). Thus, while pMGE5 seems to originate most PV-containing GABAergic neurons in the globus pallidus, it seems to produce very few PV-containing cortical interneurons.