2009;Petanjek, Kostovi, et al. In summary, COUP-TFII is expressed in the human fetal forebrain in GABAergic cells, according to its possible role in migration of cortical interneurons. The source of these cells seems to be the CGE and, to a smaller extent, the cortical VZ/SVZ. Keywords:caudal ganglionic eminence, fetal cerebral cortex, human cortical progenitors, interneurons == Introduction == Cortical interneurons are inhibitory -aminobutyric acid positive (GABAergic) cells, further subdivided by the expression of calcium-binding proteins (e.g., parvalbuminPV, calbindinCB, and calretininCalR) or neuropeptides (somatostatinSst, neuropeptide YNPY, vasoactive intestinal polypeptideVIP). They are critically involved in the formation of cortical circuitry, which is indispensable for normal brain function (Haydar et al. 2000;Owens and Kriegstein 2002;Rakic 2009;Zecevic et al. 2011). In rodents, cortical interneurons originate in the ganglionic eminence (GE) of the ventral pallium and tangentially migrate to the neocortex (Parnavelas 2000;Marn et al. 2003). The GE is a transitory embryonic structure, which consists of 3 subdivisions: lateral (LGE), medial (MGE), and caudal (CGE), based on their anatomical position and the expression of transcription factors. Two types of cells, cortical interneurons and oligodendrocytes, have been described to be generated in the GE both in rodents (Marshall and Goldman 2002) and in primates (Letinic et al. 2002;Rakic and Zecevic 2003a,2003b;Jakovcevski and Zecevic 2005a,2005b;Petanjek, Berger, et al. 2009;Petanjek, Kostovi, et al. 2009;Jakovcevski et al. 2011). In rodents, the 3 GE regions generate cortical interneurons from specific populations of progenitors, which differ in their molecular signature and their final destination (Xu et al. 2003;Butt et al. 2005;Fogarty et al. 2007). The LGE generates interneurons for the olfactory bulb and striatum. The MGE is the main source of the early-born parvalbumin-expressing (PV+) and Sst+cortical interneurons that migrate tangentially into the deep cortical layers (Wichterle et al. 2001;Marn et al. 2003;Wonders and Anderson 2006). The CGE generates late-born interneurons that migrate to the caudal neocortex, hippocampus, and amygdala (Nery et al. 2002;Butt et al. 2005). The majority of CGE-derived interneurons are CalR+or CB+bipolar cells that reside in the upper cortical layers (Xu et al. 2004;Butt et al. 2005;Sousa et al. 2009). They migrate through a caudal migratory stream either prenatally (Yozu et al. 2005;Kanatani et al. 2008) or after birth (Inta et al. 2008) under the regulation of the orphan nuclear receptor COUP-TF I/II (chicken ovalbumin upstream promoter transcription factors I and II) also known as Nr2f (Nuclear receptor subfamily 2 group F member) (Tripodi et al. 2004;Yozu et al. 2005;Kanatani et al. 2008;Miyoshi et al. 2010). In rodents, one-third of all cortical interneurons are estimated to be derived from the CGE (Nery et al. 2002;Butt et al. 2005;Miyoshi et al. 2010). In contrast to rodents, primate cortical interneurons have a prolonged generation period originating from both the cortical ventricular/subventricular zones (VZ/SVZ) and from the GE (Letinic et al. 2002;Rakic and Zecevic 2003a;Zecevic et al. 2005,Petanjek, Berger, et al. 2009;Petanjek, Kostovi, et al. 2009;Jakovcevski et al. 2011;Yu and Zecevic 2011;Zecevic et al. 2011). Furthermore, bipolar and double-bouquet Cyclosporin B CalR+cells are more numerous in human brains than in other species (Cond et al. 1994;Gabbott and Bacon 1996;Gabbott et al. 1997;Gonchar and Burkhalter 1997; Kawaguchi and Kubota 1997;DeFelipe et al. 2006,Bayatti et al. 2008). Their origin is of considerable interest for better understanding how cell circuitry is established in Cyclosporin B the human cerebral cortex. Impaired cortical circuitry and interneuron development has been implicated in numerous neurological and psychiatric disorders, from epilepsy to schizophrenia and autism Mouse monoclonal to SMN1 (e.g.,DeFelipe 1999;Lewis and Levitt 2002;Levitt 2003;Baraban and Tallent 2004). In primates, the question of the CGE as a source of cortical interneurons has not been addressed. To better characterize CGE-derived cortical internuerons, we studied the expression of COUP-TFII in the human fetal brain during the first half of the intrauterine period. This period of development in human brain coincides with interneuron genesis and their migration into emerging cortical layers (e.g.,Letinic Cyclosporin B et al. 2002;Jakovcevski et al. 2011;Zecevic et al. 2011). Our results are based largely on immunohistochemistry on fixed brain tissue sections and represent the first study to demonstrate COUP-TFII distribution in the human fetal forebrain. COUP-TFII is expressed from the earliest stage studied here (9 gestational weeks [GW]) both in the ventral (CGE) and the dorsal forebrain regions, including the cerebral cortex. COUP-TFII has nuclear expression in a subpopulation of GABA+, CalR+, and CB+cells, suggesting that some of these interneuron subtypes have CGE origin. A number of COUP-TFII+cells are still dividing, as shown by their colabeling with.