Layer Acquisition by Cortical GABAergic Interneurons Is Independent of Reelin Signaling

Abstract

Functioning of the cerebral cortex requires the coordinated assembly of circuits involving glutamatergic projection neurons and GABAergic interneurons. Despite their segregated origin in different regions of the telencephalon, projection neurons and interneurons born synchronically end up adopting the same cortical layer, suggesting that layer acquisition is highly coordinated for both neuronal types. The radial migration and laminar arrangement of projection neurons depends on Reelin, a secreted glycoprotein expressed near the pial surface during embryogenesis. In contrast, the mechanisms controlling layer acquisition by cortical interneurons remain essentially unknown. Here, we have used an ultrasound-guided transplantation approach to analyze the mechanisms underlying the acquisition of laminar locations by cortical interneurons. We found that layer acquisition by cortical GABAergic interneurons does not directly depend on Reelin signaling. Moreover, interneurons invade their target layers well after synchronically generated projection neurons reach their final destination. These results suggest a model in which cues provided by projection neurons guide cortical interneurons to their appropriate layer, and reveal that, at least for some neuronal types, long-range radial migration does not directly require Reelin.

Delineation of Multiple Subpallial Progenitor Domains by the Combinatorial Expression of Transcriptional Codes

“…High-density cell suspensions (ϳ25,000 cells/l) were front-loaded into beveled glass micropipettes (ϳ50 m diameter) prefilled with mineral oil and mounted in a pressure microinjector (Visualsonics, Toronto, Ontario, Canada), as described previously (Pla et al, 2006). Recipient pregnant females (E13.5) were anesthetized with sodium pentobarbital (0.625 mg/10 g, i.p.…”

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…The radial glia, meanwhile, are maintained by NRG1/ErbB signaling and even transient disruptions of NRG1 signaling cause these cells to differentiate prematurely, which could have a profound impact on radial migration (Schmid et al, 2003). GABAergic interneurons destined for the cortex, however, migrate tangentially over much longer distances from the subpallium, avoid the striatum via semaphorin 3A-and 3F-mediated chemorepulsion (Marin et al, 2001b), and settle into final positions after the migration of projection cells is compete (Bartolini et al, 2013;Pla et al, 2006). NRG1/ErbB interactions are necessary for GABAergic cell migration as neuregulin acts as both a local and long-range attractant cue for migrating interneurons and dysfunction of either ligand or receptor leads to deficits in cell migration and cortical patterning (Flames et al, 2004).…”

Regional Distribution of Cortical Interneurons and Development of Inhibitory Tone Are Regulated by Cxcl12/Cxcr4 Signaling

“…Next, we analyzed the distribution of calretinin and nNOS, which label interneurons with a bias in the upper and lower cortical layers, respectively (Pla et al, 2006). Although most calretininϩ cells are appropriately located in superficial layers in the Dlx5/6-cKOs (Fig.…”

“…Therefore, it appears that interneurons do have a laminar organization dependent on birthdate, but that it is not regulated in the same way as for projection neurons. Also, Reelin signaling, which regulates laminar position of projection neurons, does not appear to autonomously regulate interneuron laminar position (Pla et al, 2006). Thus, future work will need to establish how interneurons decipher where to intercalate within the cortical plate.…”