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Differential Expression of CXCL12 and CXCR4 During Human Fetal Neural Progenitor Cell Differentiation

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Abstract

Stromal cell-derived factor 1 alpha (SDF-1α, CXCL12) and its receptor CXCR4 play an important role in the central nervous system (CNS) development and adulthood by mediating cell migration, enhancing precursor cell proliferation, assisting in neuronal circuit formation, and possibly regulating migration during repair. The expression pattern of CXCR4 and CXCL12 during neurogenesis has not been thoroughly elucidated. In this study, we investigated the expression of CXCL12 and CXCR4 during neural progenitor cells (NPC) differentiation by microarray analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) using human fetal NPC as a model system. The production of CXCL12 was measured by enzyme-linked immunosorbent assay (ELISA). CXCR4 expression was determined by florescence-activated cell sorting (FACS) analysis, immunocytochemical staining, and CXCR4-mediated inhibition of cyclic AMP (cAMP) accumulation. Our data demonstrated that CXCR4 expression is significantly upregulated when NPC are differentiated into neuronal precursors, whereas CXCL12 is upregulated when differentiated into astrocytes. We also provide evidence that CXCR4 localization changes as neurons mature. In neuronal precursors, CXCR4 is localized in both neuronal processes and the cell body, whereas in mature neurons, it is primarily expressed on axons and dendrites. This differential expression of CXCR4 and CXCL12 may be important for the temporal regulation of neuronal migration and circuit formation during development and possibly in adult neurogenesis and repair.

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Acknowledgments

This work was supported in part by research grants from the National Institutes of Health: R01 NS 41858, P20 RR15635, and P01 NS043985 to JZ. We kindly acknowledge Nicholas Whitney, Dr. Anuja Ghorpade, Dr. Changhai Tian, Li Wu, and Dr. Jim Eudy (UNMC microarray core facility). Dr. Joe Zhou (UNL) provided technical support for this work. Nathan Erdmann and Yunlong Huang provided valuable comments and suggestions about the manuscript. Dr. Charles Kuszynski and Linda Wilkie performed the FACS analysis. Julie Ditter, Robin Taylor, Myhanh Che, Na Ly, and Emilie Scoggins provided outstanding administrative support.

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Authors and Affiliations

  1. Laboratory of Neurotoxicology, Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology/Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA

    Hui Peng, Ryan Kolb, J. E. Kennedy & Jialin Zheng

  2. Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA

    Jialin Zheng

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  1. Hui Peng
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  2. Ryan Kolb
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  3. J. E. Kennedy
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  4. Jialin Zheng
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Correspondence to Jialin Zheng.

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Peng, H., Kolb, R., Kennedy, J.E. et al. Differential Expression of CXCL12 and CXCR4 During Human Fetal Neural Progenitor Cell Differentiation. Jrnl Neuroimmune Pharm 2, 251–258 (2007). https://doi.org/10.1007/s11481-007-9081-3

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  • DOI: https://doi.org/10.1007/s11481-007-9081-3

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