Chemokine signaling controls intracortical migration and final distribution of GABAergic interneurons

Abstract

Functioning of the cerebral cortex requires the coordinated assembly of circuits involving glutamatergic projection neurons and GABAergic interneurons. Although much is known about the migration of interneurons from the subpallium to the cortex, our understanding of the mechanisms controlling their precise integration within the cortex is still limited. Here, we have investigated in detail the behavior of GABAergic interneurons as they first enter the developing cortex by using time-lapse videomicroscopy, slice culture, and in utero experimental manipulations and analysis of mouse mutants. We found that interneurons actively avoid the cortical plate for a period of approximately 48 h after reaching the pallium; during this time, interneurons disperse tangentially through the marginal and subventricular zones. Perturbation of CXCL12/CXCR4 signaling causes premature cortical plate invasion by cortical interneurons and, in the long term, disrupts their laminar and regional distribution. These results suggest that regulation of cortical plate invasion by GABAergic interneurons is a key event in cortical development, because it directly influences the coordinated formation of appropriate glutamatergic and GABAergic neuronal assemblies.