Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 99, Issue 10, Pages 7090-7095Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.092013799
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Funding
- NIDA NIH HHS [R01 DA013141, DA13141] Funding Source: Medline
- NIDDK NIH HHS [DK44840] Funding Source: Medline
- NIMH NIH HHS [R37 MH040165, MH59962, R01 MH059962, R37 MH059962, MH40165] Funding Source: Medline
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We investigated the role of the CXCR4 chemokine receptor in development of the mouse hippocampus. CXCR4 mRNA is expressed at sites of neuronal and progenitor cell migration in the hippocampus at late embryonic and early postnatal ages. mRNA for stromal cell-derived factor 1 (SDF-1), the only known ligand for the CXCR4 receptor, is expressed close to these migration sites, in the meninges investing the hippocampal primordium and the primordium itself. In mice engineered to lack the CXCR4 receptor, the morphology of the hippocampal dentate gyrus (DG) is dramatically altered. Gene expression markers for DG granule neurons and bromodeoxyuridine labeling of dividing cells revealed an underlying defect in the stream of postmitotic cells and secondary dentate progenitor cells that migrate toward and form the DG. In the absence of CXCR4, the number of dividing cells in the migratory stream and in the DG itself is reduced, and neurons appear to differentiate prematurely before reaching their target. Our findings indicate a role for the SDF-1/CXCR4 chemokine signaling system in DG morphogenesis. Finally, the DG is unusual as a site of adult neurogenesis. We find that both CXCR4 and SDF-1 are expressed in the adult DG, suggesting an ongoing role in DG morphogenesis.
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