Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Adhesion Molecules, Neuronal / biosynthesis
-
Cell Count
-
Cell Movement / drug effects
-
Cell Movement / physiology*
-
Chemokine CXCL12
-
Chemokines, CXC / deficiency
-
Chemokines, CXC / genetics
-
Chemokines, CXC / physiology
-
Choristoma / genetics
-
Choristoma / pathology
-
Extracellular Matrix Proteins / biosynthesis
-
Gene Expression Regulation, Developmental
-
Immunohistochemistry
-
In Situ Hybridization
-
Interneurons / cytology
-
Interneurons / metabolism*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Neocortex / abnormalities
-
Neocortex / cytology
-
Neocortex / metabolism*
-
Nerve Tissue Proteins
-
Nervous System Malformations / genetics
-
Nervous System Malformations / pathology
-
RNA, Messenger / biosynthesis
-
Rats
-
Rats, Wistar
-
Receptors, CXCR4 / deficiency
-
Receptors, CXCR4 / genetics
-
Receptors, CXCR4 / physiology*
-
Reelin Protein
-
Serine Endopeptidases
-
Signal Transduction / physiology
-
Stem Cells / cytology
-
Stem Cells / metabolism
Substances
-
Cell Adhesion Molecules, Neuronal
-
Chemokine CXCL12
-
Chemokines, CXC
-
Cxcl12 protein, mouse
-
Extracellular Matrix Proteins
-
Nerve Tissue Proteins
-
RNA, Messenger
-
Receptors, CXCR4
-
Reelin Protein
-
Serine Endopeptidases