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-TFIIþ/somatostatin (SOM)þ 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-TFIIþ neocortical interneurons, suggesting that the dMGE is the source of COUP-TFIIþ/SOMþ neocortical interneurons. We also observed a migratory stream of COUP-TFIIþ/Sp8þ 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-TFIIþ interneurons occupy cortical layer V, later-born dLGEand CGE-derived COUP-TFIIþ 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. J. Comp. Neurol. 521:479–497, 2013. VC 2012 Wiley Periodicals, Inc. INDEXING TERMS: COUP-TFII; ganglionic eminence; interneurons; neocortical development; neural progenitor cells; Sp8 About 80% of neurons in the neocortex are excitatory glutamatergic projection neurons and 20% are inhibitory GABAergic interneurons. Unlike projection neurons that originate in the ventricular zone (VZ) of the embryonic neocortex, gamma-aminobutyric acid (GABA)ergic neurons in rodents derive from the ganglionic eminences of the ventral telencephalon and tangentially migrate into the neocortex (Marin and Rubenstein, 2001; Metin et al., 2006; Wonders and Anderson, 2006; Batista-Brito and Fishell, 2009; Gelman et al., 2012). Increasing evidence suggests that defects in neocortical interneurons contribute to human neurodevelopmental disorders such as epilepsy, autism, and schizophrenia (Lewis et al., 2005; Marin, 2012). Moreover, recent studies using interneuron transplants have suggested the possibility of a cell-based therapy to modulate aberrant brain activity in the Grant sponsor: National Basic Research Program of China; Grant numbers: 2011CB504400 and 2010CB945500; Grant sponsor: National Natural Science Foundation of China; Grant numbers: 30970949, 30990261, 31028009 and 31121061; Grant sponsor: Shanghai ShuGuang Project; Grant number: 09SG05. The first two authors contributed equally to this work. *CORRESPONDENCE TO: Zhengang Yang, Ph.D., Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China. E-mail: yangz@fudan.edu.cn VC 2012 Wiley Periodicals, Inc. Received April 5, 2012; Revised June 5, 2012; Accepted July 6, 2012 DOI 10.1002/cne.23186 Published online July 13, 2012 in Wiley Online Library (wileyonlinelibrary. com) The Journal of Comparative Neurology | Research in Systems Neuroscience 521:479–497 (2013) 479 RESEARCH ARTICLE