Journal
DEVELOPMENTAL NEUROBIOLOGY
Volume 73, Issue 9, Pages 647-672Publisher
WILEY
DOI: 10.1002/dneu.22075
Keywords
axonal guidance; cerebral cortex; corpus callosum; GABAergic interneurons; guidance factors
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Funding
- Fond National Suisse [FNS 31003A-122550]
- Fondation Pierre Mercier pour la Science
- European Research Council (ERC) Starting Grant under the European Community [FP7/20072013]
- ERC [207807]
- Wellcome Trust
- MEXT, Japan
- Takeda Science Foundation
- European Research Council (ERC) [207807] Funding Source: European Research Council (ERC)
- Medical Research Council [G0501173] Funding Source: researchfish
- MRC [G0501173] Funding Source: UKRI
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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. (c) 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 647-672, 2013
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