The chemokine SDF-1 differentially regulates axonal elongation and branching in hippocampal neurons

Pujol, Fabien; Kitabgi, Patrick; Boudin, Hélène

doi:10.1242/jcs.01694

Cited by 123 publications

(92 citation statements)

References 50 publications

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“…A previous study showed that the cellular localization of CXCR4 changes during the maturation of rat hippocampal neurons (Pujol et al 2005). In this study, neuronal precursors differentiated in NB27 showed a broad expression of CXCR4 on both the cell body and neurites (Fig.…”

Section: Cellular Localization Of Cxcr4 Changes As Neurons Maturatesupporting

confidence: 60%

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

Peng

Kolb

Kennedy

et al. 2007

Jrnl Neuroimmune Pharm

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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 transcriptasepolymerase 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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Section: Cellular Localization Of Cxcr4 Changes As Neurons Maturatesupporting

confidence: 60%

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

Peng

Kolb

Kennedy

et al. 2007

Jrnl Neuroimmune Pharm

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“…[61][62][63] Potentially, such podocyte precursors of glomerular parietal epithelial cell origin may be involved in the repopulation of the glomerular tuft during podocyte injury. 58 -60,64 CXCR4/CXCL12 guide cell migration in a number of systems (eg, renal morphogenesis (tubulogenesis), neuron/ axon development, and tumor metastasis [65][66][67][68] ). Using an in vitro wound healing assay to evaluate CXCR4-dependent migration, we could demonstrate that treatment of cultured podocytes with a blocking CXCR4 antibody significantly impaired in vitro wound healing and hence CXCR4-dependent cell migration.…”

Section: Discussionmentioning

confidence: 99%

Human Nephrosclerosis Triggers a Hypoxia-Related Glomerulopathy

Neusser

Lindenmeyer

Moll

et al. 2010

The American Journal of Pathology

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In the kidney, hypoxia contributes to tubulointerstitial fibrosis, but little is known about its implications for glomerular damage and glomerulosclerosis. Chronic hypoxia was hypothesized to be involved in nephrosclerosis (NSC) or "hypertensive nephropathy." In the present study genome-wide expression data from microdissected glomeruli were studied to examine the role of hypoxia in glomerulosclerosis of human NSC. Functional annotation analysis revealed prominent regulation of hypoxia-associated biological processes in NSC, including angiogenesis, fibrosis, and inflammation. Glomerular expression levels of a majority of genes regulated by the hypoxia-inducible factors (HIFs) were significantly altered in NSC. Among these HIF targets, chemokine C-X-C motif receptor 4 (CXCR4) was prominently induced. Glomerular CXCR4 mRNA induction was confirmed by quantitative RT-PCR in an independent cohort with NSC but not in those with other glomerulopathies. By immunohistological analysis, CXCR4 showed enhanced positivity in podocytes in NSC biopsy specimens. This CXCR4 positivity was associated with nuclear localization of HIF1␣ only in podocytes of NSC, indicating transcriptional activity of HIF. As the CXCR4 ligand CXCL12/SDF-1 is constitutively expressed in podocytes, autocrine signaling may contribute to NSC. In addition, a blocking CXCR4 antibody caused significant inhibition of wound closure by podocytes in an in vitro scratch assay. These data support a role for CXCR4/CXCL12 in human NSC and indicate that hypoxia not only is involved in tubulointerstitial fibrosis but also contributes to glomerular damage in NSC. Hypoxia is considered a pivotal factor contributing to tubular atrophy and interstitial fibrosis, which are factors for the progression of renal disease. 1 The evidence in support of this hypothesis derives mostly from experimental animal studies.2-5 Most of these have focused on the tubulointerstitial space with little attention being paid to the glomerulus. The cellular response to hypoxia is largely mediated by heterodimeric transcription factors, the hypoxia-inducible factors (HIFs).2 The cellular levels of the HIF1␣ and HIF2␣ subunits (HIF␣) of HIF (gene symbols HIF1A and HIF2A) are controlled mainly by posttranslational protein modification. Under normoxia HIF␣ is degraded by the von Hippel-Lindau tumor suppressor protein. This process is regulated by oxygen-dependent hydroxylation of HIF␣ through specific prolyl hydroxylases. Under hypoxic conditions degradation of HIF␣ ceases and the stabilized protein can function as a transcription factor.2 In the renal glomerulus, a functional role of HIF1␣ 6 -8 and HIF2␣ 9 has been documented in podocytes of rodents. Recently, glomerular podocyte-specific deletion of von Hippel-Lindau tumor suppressor protein was achieved in mice, resulting in podocyte-specific overactivity of HIF with induction of HIF target genes. 6,8

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“…Rat hippocampal and cortical cultures were prepared from 18-d-old rat embryos by previously described methods (Goslin et al, 1998;Pujol et al, 2005). Briefly, hippocampi were dissected and dissociated by trypsin and trituration and plated on glass coverslips coated with poly-l-lysine.…”

Section: Cell Culturesmentioning

confidence: 99%

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

Baudouin

Angibaud

Loussouarn

et al. 2008

MBoC

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A novel idea is emerging that a large molecular repertoire is common to the nervous and immune systems, which might reflect the existence of novel neuronal functions for immune molecules in the brain. Here, we show that the transmembrane adaptor signaling protein CD3, first described in the immune system, has a previously uncharacterized role in regulating neuronal development. Biochemical and immunohistochemical analyses of the rat brain and cultured neurons showed that CD3 is mainly expressed in neurons. Distribution of CD3 in developing cultured hippocampal neurons, as determined by immunofluorescence, indicates that CD3 is preferentially associated with the somatodendritic compartment as soon as the dendrites initiate their differentiation. At this stage, CD3 was selectively concentrated at dendritic filopodia and growth cones, actin-rich structures involved in neurite growth and patterning. siRNA-mediated knockdown of CD3 in cultured neurons or overexpression of a loss-of-function CD3 mutant lacking the tyrosine phosphorylation sites in the immunoreceptor tyrosine-based activation motifs (ITAMs) increased dendritic arborization. Conversely, activation of endogenous CD3 by a CD3 antibody reduced the size of the dendritic arbor. Altogether, our findings reveal a novel role for CD3 in the nervous system, suggesting its contribution to dendrite development through ITAM-based mechanisms.

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The chemokine SDF-1 differentially regulates axonal elongation and branching in hippocampal neurons

Cited by 123 publications

References 50 publications

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

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

Human Nephrosclerosis Triggers a Hypoxia-Related Glomerulopathy

The Signaling Adaptor Protein CD3ζ Is a Negative Regulator of Dendrite Development in Young Neurons

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