PT - JOURNAL ARTICLE AU - Simona Lodato AU - Giulio Srubek Tomassy AU - Elvira De Leonibus AU - Yoryani G. Uzcategui AU - Gennaro Andolfi AU - Maria Armentano AU - Audrey Touzot AU - Jose M. Gaztelu AU - Paola Arlotta AU - Liset Menendez de la Prida AU - Michèle Studer TI - Loss of COUP-TFI Alters the Balance between Caudal Ganglionic Eminence- and Medial Ganglionic Eminence-Derived Cortical Interneurons and Results in Resistance to Epilepsy AID - 10.1523/JNEUROSCI.6580-10.2011 DP - 2011 Mar 23 TA - The Journal of Neuroscience PG - 4650--4662 VI - 31 IP - 12 4099 - http://www.jneurosci.org/content/31/12/4650.short 4100 - http://www.jneurosci.org/content/31/12/4650.full SO - J. Neurosci.2011 Mar 23; 31 AB - In rodents, cortical interneurons originate from the medial ganglionic eminence (MGE) and caudal ganglionic eminence (CGE) according to precise temporal schedules. The mechanisms controlling the specification of CGE-derived interneurons and their role in cortical circuitry are still unknown. Here, we show that COUP-TFI expression becomes restricted to the dorsal MGE and CGE at embryonic day 13.5 in the basal telencephalon. Conditional loss of function of COUP-TFI in subventricular precursors and postmitotic cells leads to a decrease of late-born, CGE-derived, VIP (vasoactive intestinal peptide)- and CR (calretinin)-expressing bipolar cortical neurons, compensated by the concurrent increase of early-born MGE-derived, PV (parvalbumin)-expressing interneurons. Strikingly, COUP-TFI mutants are more resistant to pharmacologically induced seizures, a phenotype that is dependent on GABAergic signaling. Together, our data indicate that COUP-TFI controls the delicate balance between MGE- and CGE-derived cortical interneurons by regulating intermediate progenitor divisions and ultimately affecting the activity of the cortical inhibitory circuitry.