Chemokine signaling controls intracortical migration and final distribution of GABAergic interneurons.
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.
López-Bendito
Guillermina
G
Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, 03550 Sant Joan d'Alacant, Spain.
Sánchez-Alcañiz
Juan Antonio
JA
Pla
Ramón
R
Borrell
Víctor
V
Picó
Esther
E
Valdeolmillos
Miguel
M
Marín
Oscar
O
D000818:Animals; D002450:Cell Communication; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018920:Coculture Techniques; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D005680:gamma-Aminobutyric Acid