title: Loss of COUP-TFI alters the balance between caudal ganglionic eminence- and medial ganglionic eminence-derived cortical interneurons and results in resistance to epilepsy.
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.
authors: Telethon Institute of Genetics and Medicine, Developmental Disorders Program, and European School of Molecular Medicine, 80131 Naples, Italy.
authors: Simona
authors: S
authors: Lodato
authors: Giulio Srubek
authors: GS
authors: Tomassy
authors: Elvira
authors: E
authors: De Leonibus
authors: Yoryani G
authors: YG
authors: Uzcategui
authors: Gennaro
authors: G
authors: Andolfi
authors: Maria
authors: M
authors: Armentano
authors: Audrey
authors: A
authors: Touzot
authors: Jose M
authors: JM
authors: Gaztelu
authors: Paola
authors: P
authors: Arlotta
authors: Liset
authors: L
authors: Menendez de la Prida
authors: Michèle
authors: M
authors: Studer
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D051838:COUP Transcription Factor I / Q000235:genetics* / Q000502:physiology*; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D003292:Convulsants / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D004569:Electroencephalography; D055724:Electrophysiological Phenomena; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000502:physiology*; D008473:Median Eminence / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000166:cytology / Q000502:physiology; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology; D018080:Receptors, GABA-B / Q000235:genetics / Q000502:physiology; D013687:Telencephalon / Q000166:cytology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D000963:Antimetabolites; D051838:COUP Transcription Factor I; D003292:Convulsants; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001973:Bromodeoxyuridine