title: Two specific populations of GABAergic neurons originating from the medial and the caudal ganglionic eminences aid in proper navigation of callosal axons.
abstract: The corpus callosum (CC) plays a crucial role in interhemispheric communication. It has been shown that CC formation relies on the guidepost cells located in the midline region that include glutamatergic and GABAergic neurons as well as glial cells. However, the origin of these guidepost GABAergic neurons and their precise function in callosal axon pathfinding remain to be investigated. Here, we show that two distinct GABAergic neuronal subpopulations converge toward the midline prior to the arrival of callosal axons. Using in vivo and ex vivo fate mapping we show that CC GABAergic neurons originate in the caudal and medial ganglionic eminences (CGE and MGE) but not in the lateral ganglionic eminence (LGE). Time lapse imaging on organotypic slices and in vivo analyses further revealed that CC GABAergic neurons contribute to the normal navigation of callosal axons. The use of Nkx2.1 knockout (KO) mice confirmed a role of these neurons in the maintenance of proper behavior of callosal axons while growing through the CC. Indeed, using in vitro transplantation assays, we demonstrated that both MGE- and CGE-derived GABAergic neurons exert an attractive activity on callosal axons. Furthermore, by combining a sensitive RT-PCR technique with in situ hybridization, we demonstrate that CC neurons express multiple short and long range guidance cues. This study strongly suggests that MGE- and CGE-derived interneurons may guide CC axons by multiple guidance mechanisms and signaling pathways.
authors: Département des neurosciences fondamentales, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland.
authors: Mathieu
authors: M
authors: Niquille
authors: Shilpi
authors: S
authors: Minocha
authors: Jean-Pierre
authors: JP
authors: Hornung
authors: Nathalie
authors: N
authors: Rufer
authors: Delphine
authors: D
authors: Valloton
authors: Nicoletta
authors: N
authors: Kessaris
authors: Fabienne
authors: F
authors: Alfonsi
authors: Tania
authors: T
authors: Vitalis
authors: Yuchio
authors: Y
authors: Yanagawa
authors: Christiane
authors: C
authors: Devenoges
authors: Alexandre
authors: A
authors: Dayer
authors: Cécile
authors: C
authors: Lebrand
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D003337:Corpus Callosum / Q000196:embryology* / Q000648:ultrastructure; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology* / Q000648:ultrastructure; D066298:In Vitro Techniques; D007395:Interneurons / Q000166:cytology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics; D013687:Telencephalon / Q000166:cytology / Q000196:embryology; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics
chemical_list: C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
keywords: GABAergic interneurons; axonal guidance; cerebral cortex; corpus callosum; guidance factors