Semaphorin 3C guides MGE-derived cortical interneurons through the basal telencephalon

While it is known that Semaphorins act as guidance cues for growing axons during brain development (Bagnard, Lohrum et al. 1998, Ruediger, Zimmer et al. 2013), their potential role during interneuron migration is largely unknown. One striking observation is that Sema3C demarcates the pallial/subpallial border and the intracortical pathway of cortical interneurons in the dorsal telencephalon (Bagnard, Lohrum et al. 1998, Ruediger, Zimmer et al. 2013). Moreover, migrating cortical interneurons express Nrp1 and Nrp2, described receptors for Sema3A and Sema3C. All these reasons prompt to examine possible roles for Sema3C on cortical interneuron migration. Our main results indicated that cortical interneurons, in the deep migratory stream, encountering the increasing gradient of Sema3C seem to be attracted by this cue towards the neocortex. A novel observation from the present study is that decreasing Sema3A gradients stimulated interneurons from VZ/SVZ explants out of the MGE to move longer distances away from the Sema3A source. Moreover, Sema3A acts as a repellent cue for interneurons from the intermediate zone (IMZ) of the MGE. In contrast, only Sema3C increasing gradients attracted MGE-derived neurons specifically from the VZ/SVZ and not from the IMZ, whereas decreasing Sema3C gradients seems to have no effect.

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