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Articles, Development/Plasticity/Repair

Loss of COUP-TFI Alters the Balance between Caudal Ganglionic Eminence- and Medial Ganglionic Eminence-Derived Cortical Interneurons and Results in Resistance to Epilepsy

Simona Lodato, Giulio Srubek Tomassy, Elvira De Leonibus, Yoryani G. Uzcategui, Gennaro Andolfi, Maria Armentano, Audrey Touzot, Jose M. Gaztelu, Paola Arlotta, Liset Menendez de la Prida and Michèle Studer
Journal of Neuroscience 23 March 2011, 31 (12) 4650-4662; https://doi.org/10.1523/JNEUROSCI.6580-10.2011
Simona Lodato
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Giulio Srubek Tomassy
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Elvira De Leonibus
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Yoryani G. Uzcategui
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Gennaro Andolfi
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Maria Armentano
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Audrey Touzot
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Jose M. Gaztelu
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Paola Arlotta
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Liset Menendez de la Prida
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Michèle Studer
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Abstract

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.

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The Journal of Neuroscience: 31 (12)
Journal of Neuroscience
Vol. 31, Issue 12
23 Mar 2011
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Loss of COUP-TFI Alters the Balance between Caudal Ganglionic Eminence- and Medial Ganglionic Eminence-Derived Cortical Interneurons and Results in Resistance to Epilepsy
Simona Lodato, Giulio Srubek Tomassy, Elvira De Leonibus, Yoryani G. Uzcategui, Gennaro Andolfi, Maria Armentano, Audrey Touzot, Jose M. Gaztelu, Paola Arlotta, Liset Menendez de la Prida, Michèle Studer
Journal of Neuroscience 23 March 2011, 31 (12) 4650-4662; DOI: 10.1523/JNEUROSCI.6580-10.2011

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Loss of COUP-TFI Alters the Balance between Caudal Ganglionic Eminence- and Medial Ganglionic Eminence-Derived Cortical Interneurons and Results in Resistance to Epilepsy
Simona Lodato, Giulio Srubek Tomassy, Elvira De Leonibus, Yoryani G. Uzcategui, Gennaro Andolfi, Maria Armentano, Audrey Touzot, Jose M. Gaztelu, Paola Arlotta, Liset Menendez de la Prida, Michèle Studer
Journal of Neuroscience 23 March 2011, 31 (12) 4650-4662; DOI: 10.1523/JNEUROSCI.6580-10.2011
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