CXCL12/CXCR4 signalling in neuronal cell migration

Tiveron, Marie-Catherine; Cremer, Harold

doi:10.1016/j.conb.2008.06.004

Cited by 99 publications

(82 citation statements)

References 46 publications

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“…A canonical route of signalling for CXCR7 has not been described and indeed the capacity to activate secondary messenger systems has been questioned. Thus some studies have provided evidence that CXCR7 represents a silent or decoy receptor responsible for either sequestering extracellular CXCL12 Tiveron and Cremer, 2008) or modulating CXCR4 signalling by forming heterodimers (Levoye et al, 2009;Sierro et al, 2007). Although virtually all reports have agreed that CXCR7 does not couple to G proteins, functional roles for the receptor that belie a signalling event suggest a non-classical positive signalling role for this …”

Section: Discussionmentioning

confidence: 99%

CXCL12 receptor preference, signal transduction, biological response and the expression of 5T4 oncofoetal glycoprotein

McGinn

Marinov

Sawan

et al. 2012

Journal of Cell Science

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SummaryCXCL12 is a pleiotropic chemokine capable of eliciting multiple signal transduction cascades and functions, via interaction with either CXCR4 or CXCR7. Factors that determine CXCL12 receptor preference, intracellular signalling route and biological response are poorly understood but are of central importance in the context of therapeutic intervention of the CXCL12 axis in multiple disease states. We have recently demonstrated that 5T4 oncofoetal glycoprotein facilitates functional CXCR4 expression leading to CXCL12 mediated chemotaxis in mouse embryonic cells. Using wild type (WT) and 5T4 knockout (5T4KO) murine embryonic fibroblasts (MEFs), we now show that CXCL12 binding to CXCR4 activates both the ERK and AKT pathways within minutes, but while these pathways are intact, they are non-functional in 5T4KO cells treated with CXCL12. Importantly, in the absence of 5T4 expression, CXCR7 is upregulated and becomes the predominant receptor for CXCL12, activating a distinct signal transduction pathway with slower kinetics involving transactivation of the epidermal growth factor receptor (EGFR), eliciting proliferation rather than chemotaxis. Thus the surface expression of 5T4 marks the use of the CXCR4 rather than the CXCR7 receptor, with distinct consequences for CXCL12 exposure, relevant to the spread and growth of a tumour. Consistent with this hypothesis, we have identified human small cell lung carcinoma cells with similar 5T4/CXCR7 reciprocity that is predictive of biological response to CXCL12 and determined that 5T4 expression is required for functional chemotaxis in these cells.

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Section: Discussionmentioning

confidence: 99%

CXCL12 receptor preference, signal transduction, biological response and the expression of 5T4 oncofoetal glycoprotein

McGinn

Marinov

Sawan

et al. 2012

Journal of Cell Science

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“…Reduced Cxcr4 expression in LgDel migrating interneuronsbased upon mRNA and protein measurements-places cytokine regulation of interneuron migration via Cxcr4 (21)(22)(23)(24)(25) squarely in the context of cortical circuit disorder pathogenesis. There are several similarities between interneuron defects in LgDel and Cxcr4 −/− embryos.…”

Section: Discussionmentioning

confidence: 99%

“…Altered Cxcr4 expression and activity and the similarity of LgDel and Cxcr4 −/− interneuron phenotypes (21)(22)(23)(24)(25) suggest that diminished 22q11.2 gene dosage and disrupted Cxcr4 signaling compromise similar aspects of interneuron migration, particularly the distribution of cells in the MZ, SVZ, and VZ migratory streams. If so, one would expect further diminished Cxcr4 expression to modify distinct aspects of the LgDel interneuron phenotype selectively and proportionately.…”

Section: Diminished Cxcr4 Dosage Modifies Distribution Of Migrating Lmentioning

confidence: 99%

“…We now report in the LgDel mouse-in which recent studies (18)(19)(20) suggest that cortical circuit assembly and function is compromised-a mechanistic relationship between diminished 22q11.2 dosage and a key molecular pathway that regulates interneuron migration during cortical development. LgDel interneuron phenotypes reflect interneuron-specific disruption of cytokine receptor Cxcr4, which has been shown to influence placement, migratory trajectory, and motility of these cells during cortical development (21)(22)(23)(24)(25). Thus, we define a relationship between 22q11.2DS, a compelling example of a copy number variant (CNV) syndrome thought to cause cortical circuit disorders, and Cxcr4-mediated signaling, an established mechanism that ensures normal cortical interneuron development.…”

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confidence: 99%

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Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome

Meechan

Tucker

Maynard

et al. 2012

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

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Interneurons are thought to be a primary pathogenic target for several behavioral disorders that arise during development, including schizophrenia and autism. It is not known, however, whether genetic lesions associated with these diseases disrupt established molecular mechanisms of interneuron development. We found that diminished 22q11.2 gene dosage-the primary genetic lesion in 22q11.2 deletion syndrome (22q11.2 DS)-specifically compromises the distribution of early-generated parvalbumin-expressing interneurons in the Large Deletion (LgDel) 22q11.2DS mouse model. This change reflects cellautonomous disruption of interneuron migration caused by altered expression of the cytokine C-X-C chemokine receptor type 4 (Cxcr4), an established regulator of this process. Cxcr4 is specifically reduced in LgDel migrating interneurons, and genetic analysis confirms that diminished Cxcr4 alters interneuron migration in LgDel mice. Thus, diminished 22q11.2 gene dosage disrupts cortical circuit development by modifying a critical molecular signaling pathway via Cxcr4 that regulates cortical interneuron migration and placement.

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“…One CXC-type ligand, SDF1, plays an important role in gastrulation (Fukui et al 2007;Mizoguchi et al 2008;Nair & Schilling 2008), and SDF interacts with CXCR4 and CXCR7 (Valentin et al 2007;Tiveron & Cremer 2008). We investigated whether CXCR4 and CXCR7 interact with XCXCLC.…”

Section: Receptors For Xcxclcmentioning

confidence: 99%

Chemokine ligand Xenopus CXCLC (XCXCLC) regulates cell movements during early morphogenesis

Goto¹,

Asashima²

2011

Development, Growth &Amp; Differentiation

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We cloned the gene for the CXC-type chemokine ligand, Xenopus CXCLC (XCXCLC), the transcripts of which were detected at the dorsal midline during the gastrula and neurula stages. XCXCLC overexpression resulted in the attraction of nearby mesodermal cells, and the excess of chemoattractant interfered with convergent and extension movements. The direction of the deep neural plate cells around the notoplate was also controlled by XCXCLC. Fluorescence signals for XCXCLC + enhanced green fluorescent protein derivatives accumulated around the notochord region. These results indicate that XCXCLC attracts adjacent cells to the midline region, so as to ensure accurate lateral-medial directional tissue convergence during gastrulation and neurulation.

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CXCL12/CXCR4 signalling in neuronal cell migration

Cited by 99 publications

References 46 publications

CXCL12 receptor preference, signal transduction, biological response and the expression of 5T4 oncofoetal glycoprotein

CXCL12 receptor preference, signal transduction, biological response and the expression of 5T4 oncofoetal glycoprotein

Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome

Chemokine ligand Xenopus CXCLC (XCXCLC) regulates cell movements during early morphogenesis

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