Stromal cell‐derived factor 1‐mediated CXCR4 signaling in rat and human cortical neural progenitor cells

Abstract

Stromal cell-derived factor 1 (SDF-1) and the chemokine receptor CXCR4 are highly expressed in the nervous system. Knockout studies have suggested that both SDF-1 and CXCR4 play essential roles in cerebellar, hippocampal, and neocortical neural cell migration during embryogenesis. To extend these observations, CXCR4 signaling events in rat and human neural progenitor cells (NPCs) were examined. Our results show that CXCR4 is expressed in abundance on rat and human NPCs. Moreover, SDF-1alpha induced increased NPCs levels of inositol 1,4,5-triphosphate, extracellular signal-regulated kinases 1/2, Akt, c-Jun N-terminal kinase, and intracellular calcium whereas it diminished cyclic adenosine monophosphate. Finally, SDF-1alpha can induce human NPC chemotaxis in vitro, suggesting that CXCR4 plays a functional role in NPC migration. Both T140, a CXCR4 antagonist, and pertussis toxin (PTX), an inactivator of G protein-coupled receptors, abrogated these events. Ultimately, this study suggested that SDF-1alpha can influence NPC function through CXCR4 and that CXCR4 is functional on NPC.

Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain

“…Indeed, it is now clear that the SDF-1/CXCR4 system is widely expressed by neurons throughout the nervous system and possibly by glial elements as well (Banisadr et al, 2002a(Banisadr et al, , 2003Stumm et al, 2002;Tran and Miller, 2003;Dziembowska et al, 2005). The patterns of expression of the other chemokine receptors in the areas we examined are similar, consistent with previous findings that neural progenitor cells express numerous different chemokine receptor types (Peng et al, 2004;Tran et al, 2004;Pluchino et al, 2005). However, apart from CXCR4 there have been few large-scale anatomical studies on the distribution of chemokine receptors in the brain.…”

“…Examination of the expression patterns of SDF-1 and CXCR4 during embryogenesis (McGrath et al, 1999;Stumm et al, 2002;Tissir et al, 2004) indicates that all of these developmental phenotypes can be explained on the basis of deficits in SDF-1 mediated attraction of embryonic neural stem/progenitor cells. In keeping with this possibility, examination of embryonic neural progenitor cells in culture has confirmed that these cells express CXCR4 receptors and that SDF-1 can act as a chemoattractant (Ji et al, 2004;Krathwohl and Kaiser, 2004;Ni et al, 2004;Peng et al, 2004;Tran et al, 2004). In addition to CXCR4, the CXCR2 chemokine receptor has been shown to be important for regulating the migration of oligodendrocyte progenitor cells in the developing spinal cord (Tsai et al, 2002).…”

“…In the nervous system, SDF-1/CXCR4 signaling directs the migration of neural stem cells to a number of different parts of the brain (Zou et al, 1998;Bagri et al, 2002;Lu et al, 2002;Stumm et al, 2003) and the DRG (Belmadani et al, 2005) and also plays a role as an axonal guidance cue (Xiang et al, 2002;Arakawa et al, 2003;Chalasani et al, 2003;Lieberam et al, 2005;Pujol et al, 2005). It has also been demonstrated that neurospheres prepared from postnatal brains express CXCR4 as well as other chemokine receptors (Lazarini et al, 2000;Stumm et al, 2003;Ji et al, 2004;Peng et al, 2004;Tran et al, 2004) and that chemokines act as chemoattractants for these cells (Pluchino et al, 2005;Tran et al, 2004Tran et al, , 2005Widera et al, 2004), suggesting that chemokine-mediated effects may also be important in the regulation of adult progenitor cell migration. However, it is not known whether chemokine receptors are normally expressed by neural progenitor cells in the postnatal brain.…”

Stromal Cell-Derived Factor 1α Mediates Neural Progenitor Cell Motility after Focal Cerebral Ischemia

“…Both SDF-1a and CXCR 4 are expressed by multiple cell types of neural lineage, including NPCs of SVZ origin in the mouse and human (Peng et al, 2004). Stromal cell-derived factor 1a may also play an important role in neural progenitor migration (Tran et al, 2004;Peng et al, 2004). To our knowledge, only one other group has reported on the relevance of SDF-1a to strokeinduced NPC migration and proliferation (Imitola et al, 2004) and more research is warranted.…”

Compensatory Neurogenesis in the Injured Adult Brain

“…The SDF-1 receptors CXCR4 and CXCR7 are highly expressed on neural progenitor cells. SDF-1 expression is highly upregulated in reactive astrocytes, microglia and endothelial cells in the ischemic striatum during several weeks after focal ischemic injury and has been shown to induce the migration of progenitor cells in vitro (Peng, et al, 2004) and in vivo to areas of hypoxic-ischemic-induced inflammation via CXCR4 signalling pathways (Imitola, et al, 2004, Robin, et al, 2006. The chemokine MCP-1 is also up-regulated in response to inflammation and induces the migration of neural progenitor cells.…”