<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Abe, Philipp</dc:creator>
  <dc:creator>Mueller, Wiebke</dc:creator>
  <dc:creator>Schütz, Dagmar</dc:creator>
  <dc:creator>MacKay, Fabienne</dc:creator>
  <dc:creator>Thelen, Marcus</dc:creator>
  <dc:creator>Zhang, Penglie</dc:creator>
  <dc:creator>Stumm, Ralf</dc:creator>
  <dc:date>2014-04-09</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">The CXCL12/CXCR4 signaling pathway is involved in the development of numerous  neuronal and non-neuronal structures. Recent work established that the atypical  second CXCL12 receptor, CXCR7, is essential for the proper migration of interneuron  precursors in the developing cerebral cortex. Two CXCR7-mediated functions were  proposed in this process: direct modulation of β-arrestin-mediated signaling cascades  and CXCL12 scavenging to regulate local chemokine availability and ensure  responsiveness of the CXCL12/CXCR4 pathway in interneurons. Neither of these  functions has been proven in the embryonic brain. Here, we demonstrate that  migrating interneurons efficiently sequester CXCL12 through CXCR7. CXCR7 ablation  causes excessive phosphorylation and downregulation of CXCR4 throughout the  cortex in mice expressing CXCL12, but not in CXCL12-deficient animals. Cxcl12−/−  mice lack activated CXCR4 in embryonic brain lysates and display a similar  interneuron positioning defect as Cxcr4−/−, Cxcr7−/− and Cxcl12−/−;Cxcr7−/−  animals. Thus, CXCL12 is the only CXCR4-activating ligand in the embryonic brain  and deletion of one of the CXCL12 receptors is sufficient to generate a migration  phenotype that corresponds to the CXCL12-deficient pathway. Our findings imply that  interfering with the CXCL12-scavenging activity of CXCR7 causes loss of CXCR4  function as a consequence of excessive CXCL12-mediated CXCR4 activation and  degradation.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://n2t.net/ark:/12658/srd1318866</dc:identifier>
  <dc:identifier>https://susi.usi.ch/global/documents/318866</dc:identifier>
  <dc:identifier>https://susi.usi.ch/documents/318866/files/Abe_D_2014.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1242/dev.104224</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/ark/12658/srd1318866</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>Rights reserved</dc:rights>
  <dc:source>Development. - 2014, vol. 141, no. 9, p. 1857-1863</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">CXCL12</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">CXCR4</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">CXCR7 (ACKR3)</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Interneuron migration</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Atypical chemokine receptor</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">Cortical development</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">Mouse</dc:subject>
  <dc:subject xmlns:ns8="xml" ns8:lang="en">Cajal-Retzius cell</dc:subject>
  <dc:subject>info:eu-repo/classification/udc/61</dc:subject>
  <dc:title xmlns:ns9="xml" ns9:lang="en">CXCR7 prevents excessive CXCL12-mediated downregulation of CXCR4 in migrating cortical interneurons</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>