Abstract
CXC chemokine receptor CXCR4 is expressed in vitro in both human and rodent adult neural progenitor cells (NPCs). It has been suggested that the CXCL12-CXCR4 axis potentially enhances the proliferation of NPCs. However, whether CXCR4 is expressed in the neural stem cells (NSCs), a subset of self-renewing and multipotent NPCs, and whether CXCR4 signaling is directly required for their proliferation are not clear. In this study, we report that CXCR4 is expressed in a subpopulation of NPCs in the early embryonic ventricular zone. In studies of a CXCR4eGFP bacterial artificial chromosomal (BAC) transgenic mouse line, we further isolated NPCs from E12.5 transgenic telencephalon and GFP+ cells demonstrated self-renewal and multipotency in neurosphere assays in vitro. Consistent with these observations, we enriched GFP+/CXCR4+ cells by fluorescence activated cell sorting (FACS) with either CXCR4 antibody 12G5 or GFP. Furthermore, we observed that CXCL12 alone did not activate the self-renewal of NPCs or increase the proliferation of NPCs that are induced by bFGF/EGF. However, we found that blocking CXCR4 receptor with antagonist AMD3100 impaired the bFGF/EGF-induced expansion of GFP+ NPCs through modulating their cell cycling. In addition, AMD3100 treatment of pregnant mice reduced the generation of neurospheres from E12.5 embryos. Our data suggest that CXCR4 is a potential cell surface marker for early embryonic NSCs and modulates growth-factor signaling.
Original language | English (US) |
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Pages (from-to) | 108-118 |
Number of pages | 11 |
Journal | GLIA |
Volume | 59 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2011 |
Externally published | Yes |
Keywords
- CXCL12
- CXCR4
- Cell cycling
- Neural progenitor cells
- Proliferation
ASJC Scopus subject areas
- Neurology
- Cellular and Molecular Neuroscience