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Publication : Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor.

First Author  Lu M Year  2002
Journal  Proc Natl Acad Sci U S A Volume  99
Issue  10 Pages  7090-5
PubMed ID  11983855 Mgi Jnum  J:81783
Mgi Id  MGI:2450003 Doi  10.1073/pnas.092013799
Citation  Lu M, et al. (2002) Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci U S A 99(10):7090-5
abstractText  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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