Elsevier

Neuroscience Letters

Volume 398, Issue 3, 8 May 2006, Pages 291-295
Neuroscience Letters

SDF1α/CXCR4 signaling stimulates β-catenin transcriptional activity in rat neural progenitors

https://doi.org/10.1016/j.neulet.2006.01.024Get rights and content

Abstract

Stromal cell-derived factor (SDF-1), by activating its cognate receptor CXCR4, plays multiple roles in cell migration, proliferation and survival in the development of the central nervous system. Recently, we have shown that functional SDF1α/CXCR4 signaling mediates chemotaxis through extracellular signal-regulated kinase (ERK) activation in the developing spinal cord. Here, we report that SDF1α/CXCR4 signaling activates β-catenin/TCF transcriptional activity in embryonic rat spinal cord neural progenitors. Stimulation of neural progenitors with SDF1α resulted in cytoplasmic β-catenin accumulation in 30 min, and lasted for approximately 240 min, while Wnt3a, a positive control, stabilized cytoplasmic β-catenin in 120 min. Dose–response studies indicated that the β-catenin stabilization effect could be detected in cells exposed to fM concentrations of SDF1α. This SDF1α-induced β-catenin stabilization effect was inhibited by pretreatment of the cells with either pertussis toxin (PTX), an inactivator of G protein-coupled receptors, or PD98059, a MEK1 inhibitor. Concomitant with β-catenin accumulation in the cytoplasm, SDF1α enhanced nuclear translocation of β-catenin and its binding to nuclear transcription factor T cell-specific transcription factor/lymphoid enhancer-binding factor (TCF/LEF). Furthermore, SDF1α increased expression of genes such as Ccnd1, 2, 3, and c-Myc known as targets of the Wnt/β-catenin/TCF pathway. The increased expression of Ccnd1 and c-Myc by SDF1α was further confirmed by immunoblot analysis. Our data suggest that SDF1α/CXCR4 signaling may interact with the Wnt/β-catenin/TCF pathway to regulate the development of the central nervous system.

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Acknowledgements

This research was supported by the National Institute on Aging Intramural Research Program, NIH, the ALS Center at Johns Hopkins, the CNS Foundation and the NIH stem cell center. MSR acknowledges the contributions of Dr. S. Rao that made undertaking this project possible.

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