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The Journal of Neuroscience, June 15, 2003, 23(12):5123-5130
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CXCR4 Regulates Interneuron Migration in the Developing Neocortex
Ralf K. Stumm,1 Chun Zhou,1 Toshiaki Ara,2 Françoise Lazarini,3 Monique Dubois-Dalcq,3 Takashi Nagasawa,2 Volker Höllt,1 andStefan Schulz1 1Department of Pharmacology and Toxicology, Otto-von-Guericke University, 39120 Magdeburg, Germany, 2Department of Medical System Control, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan, and 3Unité de Neurovirologie et Régéneration du Système Nerveux, Department of Neuroscience, Institut Pasteur, 75724, Cedex 15, Paris, France
The chemotactic factors directing interneuron migration during cerebrocortical development are essentially unknown. Here we identify the CXC chemokine receptor 4 (CXCR4) in interneuron precursors migrating from the basal forebrain to the neocortex and demonstrate that stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for isolated striatal precursors. In addition, we show that CXCR4 is present in early generated Cajal-Retzius cells of the cortical marginal zone. In mice with a null mutation in CXCR4 or SDF-1, interneurons were severely underrepresented in the superficial layers and ectopically placed in the deep layers of the neocortex. In contrast, the submeningeal positioning of Cajal-Retzius cells was unaffected. Thus, our findings suggest that SDF-1, which is highly expressed in the embryonic leptomeninx, selectively regulates migration and layer-specific integration of CXCR4-expressing interneurons during neocortical development.
Key words: CXC chemokine; stromal cell-derived factor-1; CXCR4; cerebral cortex; development; reelin; Cajal-Retzius cell; hippocampus; interneuron migration; immunocytochemistry; in situ hybridization
Received Jan. 22, 2003; revised Jan. 22, 2003; accepted Mar. 13, 2003.
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