CXCR4 regulates interneuron migration in the developing neocortex.
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.
Stumm
Ralf K
RK
Department of Pharmacology and Toxicology, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Zhou
Chun
C
Ara
Toshiaki
T
Lazarini
Françoise
F
Dubois-Dalcq
Monique
M
Nagasawa
Takashi
T
Höllt
Volker
V
Schulz
Stefan
S
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D002828:Choristoma / Q000235:genetics / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009421:Nervous System Malformations / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D000091042:Reelin Protein; D012697:Serine Endopeptidases