Stromal cell derived factor-1 acutely promotes neural progenitor cell proliferation in vitro by a mechanism involving the ERK1/2 and PI-3K signal pathways☆

Gong, Xiaoming; He, Xijing; Qi, Lei; Zuo, Huancong; Xie, Zhihui

doi:10.1016/j.cellbi.2006.01.007

Cited by 40 publications

(35 citation statements)

References 21 publications

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“…As activated microglia and astrocytes were both sources of CXCL12, it is possible that alterations in the inflammatory response of one or both of these cell types contributes to remyelination failure in the setting of chronic CPZ exposure. Prior in vitro studies reported that CXCL12 promotes the proliferation of neural progenitor cells but has minimal effects on OPCs (17,30). In our study, CXCR4 antagonism led to increased proliferation in OPCs within SVZ but not within the remyelinating CC.…”

Section: Discussionsupporting

confidence: 55%

CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination

Patel

McCandless

Dorsey

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

209

206

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Multiple sclerosis is a neurodegenerative disease characterized by episodes of autoimmune attack of oligodendrocytes leading to demyelination and progressive functional deficits. Because many patients exhibit functional recovery in between demyelinating episodes, understanding mechanisms responsible for repair of damaged myelin is critical for developing therapies that promote remyelination and prevent disease progression. The chemokine CXCL12 is a developmental molecule known to orchestrate the migration, proliferation, and differentiation of neuronal precursor cells within the developing CNS. Although studies suggest a role for CXCL12 in oligodendroglia ontogeny in vitro, no studies have investigated the role of CXCL12 in remyelination in vivo in the adult CNS. Using an experimental murine model of demyelination mediated by the copper chelator cuprizone, we evaluated the expression of CXCL12 and its receptor, CXCR4, within the demyelinating and remyelinating corpus callosum (CC). CXCL12 was significantly up-regulated within activated astrocytes and microglia in the CC during demyelination, as were numbers of CXCR4+ NG2+ oligodendrocyte precursor cells (OPCs). Loss of CXCR4 signaling via either pharmacological blockade or in vivo RNA silencing led to decreased OPCs maturation and failure to remyelinate. These data indicate that CXCR4 activation, by promoting the differentiation of OPCs into oligodendrocytes, is critical for remyelination of the injured adult CNS.M ultiple sclerosis (MS), a progressive, neurodegenerative disease of the CNS, occurs most often in a relapsing/remitting form, in which a period of demyelination is followed by a period of functional recovery (1). The recovery stage involves remyelination via the migration and maturation of oligodendrocyte precursor cells (OPCs) (2). However, as the disease progresses, remyelination fails with continuous loss of function (3). Possible explanations for remyelination failure of intact axons include defects in OPC recruitment to the site of demyelination or in OPC differentiation into myelinating oligodendrocytes. Although studies indicate that both aspects of OPC biology are altered in MS (4, 5), the molecular mechanisms that orchestrate these processes within the adult CNS are incompletely understood.Studies in mice indicate that neural precursors that give rise to cells of oligodendrocytes lineage can be identified within the ventral half of the ventricular zones of all CNS regions by embryonic days 12-14 (E12-E14) via their expression of NG2 chondroitin sulfate proteoglycan (6). In the final stage of oligodendrocyte differentiation, which occurs primarily during the postnatal period (P4-P12), OPCs begin to express mature markers of oligodendrocytes including 2′3′-cyclic nucleotide phosphohydrolase (CNPase), myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). Similar events occur during remyelination; NG2+ OPCs proliferate within subventricular zones, migrate to areas of demyelination, and differentiate ...

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Section: Discussionsupporting

confidence: 55%

CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination

Patel

McCandless

Dorsey

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

209

206

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“…CXCR4 and other chemokine receptors have been reported in cultured human and rodent NPCs (Corti et al, 2005;Dziembowska et al, 2005;Gong et al, 2006;Peng et al, 2004;Tran et al, 2004;Wu et al, 2009). In vitro studies showed that CXCR4 regulates the migration and proliferation of cultured NPCs (Corti et al, 2005;Gong et al, 2006;Peng et al, 2004;Tran et al, 2004;Wu et al, 2009). Consistent with this hypothesis, conditional knockout of the CXCR4 gene caused abnormal development of the secondary neurogenic region in the mouse brain, possibly due to abnormal migration of NPCs from the ventricular zone ).…”

Section: Introductionmentioning

confidence: 53%

“…Previous studies suggested a proliferative effect of CXCL12 for human and rodent NPCs in vitro (Corti et al, 2005;Gong et al, 2006;Tran et al, 2004). We further tested whether CXCL12 is directly involved in the growth of NPCs.…”

Section: Growth Factors (But Not Cxcl12) Induce the Growth Of Npcsmentioning

confidence: 98%

“…CXCR4 mRNA is also expressed in the late development of ventricular/subventricular zone (Stumm et al, 2003(Stumm et al, , 2007Tissir et al, 2004) as well as in adult neurogenic regions (Tran et al, 2007). CXCR4 and other chemokine receptors have been reported in cultured human and rodent NPCs (Corti et al, 2005;Dziembowska et al, 2005;Gong et al, 2006;Peng et al, 2004;Tran et al, 2004;Wu et al, 2009). In vitro studies showed that CXCR4 regulates the migration and proliferation of cultured NPCs (Corti et al, 2005;Gong et al, 2006;Peng et al, 2004;Tran et al, 2004;Wu et al, 2009).…”

Section: Introductionmentioning

confidence: 96%

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Chemokine receptor CXCR4 signaling modulates the growth factor‐induced cell cycle of self‐renewing and multipotent neural progenitor cells

Chang

Lathia

et al. 2010

Glia

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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 CXCR4(eGFP) 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.

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“…Exposure of CXCL12 to quiescent NPCs enhances proliferation, promotes chain migration and transmigration (Imitola J et al, 2004). CXCL12 enhances the proliferation of NPCs in vitro, dependent on the ERK1/2 and PI-3 kinase pathways (Gong X et al, 2006). CXCL12 may promote survival, but also maintains NPCs in a quiescent state (Krathwohl MD and Kaiser JL, 2004).…”

Section: Roles Of Cxcl12/cxcr4 In Neural Progenitor Cells (Npcs)mentioning

confidence: 99%

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

Ransohoff

2008

Progress in Neurobiology

307

245

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Chemotactic cytokines (chemokines) have been traditionally defined as small (10-14 kDa) secreted leukocyte chemoattractants. However, chemokines and their cognate receptors are constitutively expressed in the central nervous system (CNS) where immune activities are under stringent control. Why and how the CNS uses the chemokine system to carry out its complex physiological functions has intrigued neurobiologists. Here, we focus on chemokine CXCL12 and its receptor CXCR4 that have been widely characterized in peripheral tissues and delineate their main functions in the CNS. Extensive evidence supports CXCL12 as a key regulator for early development of the CNS. CXCR4 signaling is required for the migration of neuronal precursors, axon guidance/pathfinding and maintenance of neural progenitor cells (NPCs). In the mature CNS, CXCL12 modulates neurotransmission, neurotoxicity and neuroglial interactions. Thus, chemokines represent an inherent system that helps establish and maintain CNS homeostasis. In addition, growing evidence implicates altered expression of CXCL12 and CXCR4 in the pathogenesis of CNS disorders such as HIVassociated encephalopathy, brain tumor, stroke and multiple sclerosis (MS), making them the plausible targets for future pharmacological intervention.

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Stromal cell derived factor-1 acutely promotes neural progenitor cell proliferation in vitro by a mechanism involving the ERK1/2 and PI-3K signal pathways☆

Cited by 40 publications

References 21 publications

CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination

CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination

Chemokine receptor CXCR4 signaling modulates the growth factor‐induced cell cycle of self‐renewing and multipotent neural progenitor cells

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

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