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Publication : EphA/ephrin A reverse signaling promotes the migration of cortical interneurons from the medial ganglionic eminence.

First Author  Steinecke A Year  2014
Journal  Development Volume  141
Issue  2 Pages  460-71
PubMed ID  24381199 Mgi Jnum  J:206575
Mgi Id  MGI:5551518 Doi  10.1242/dev.101691
Citation  Steinecke A, et al. (2014) EphA/ephrin A reverse signaling promotes the migration of cortical interneurons from the medial ganglionic eminence. Development 141(2):460-71
abstractText  Inhibitory interneurons control the flow of information and synchronization in the cerebral cortex at the circuit level. During embryonic development, multiple subtypes of cortical interneurons are generated in different regions of the ventral telencephalon, such as the medial and caudal ganglionic eminence (MGE and CGE), as well as the preoptic area (POA). These neurons then migrate over long distances towards their cortical target areas. Diverse families of diffusible and cell-bound signaling molecules, including the Eph/ephrin system, regulate and orchestrate interneuron migration. Ephrin A3 and A5, for instance, are expressed at the borders of the pathway of MGE-derived interneurons and prevent these cells from entering inappropriate regions via EphA4 forward signaling. We found that MGE-derived interneurons, in addition to EphA4, also express ephrin A and B ligands, suggesting Eph/ephrin forward and reverse signaling in the same cell. In vitro and in vivo approaches showed that EphA4-induced reverse signaling in MGE-derived interneurons promotes their migration and that this effect is mediated by ephrin A2 ligands. In EphA4 mutant mice, as well as after ephrin A2 knockdown using in utero electroporation, we found delayed interneuron migration at embryonic stages. Thus, besides functions in guiding MGE-derived interneurons to the cortex through forward signaling, here we describe a novel role of the ephrins in driving these neurons to their target via reverse signaling.
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