CXCR7 Receptor Controls the Maintenance of Subpial Positioning of Cajal-Retzius Cells

Cereb Cortex. 2015 Oct;25(10):3446-57. doi: 10.1093/cercor/bhu164. Epub 2014 Aug 1.


Cajal-Retzius (CR) cells are essential for cortical development and lamination. These pioneer neurons arise from distinct progenitor sources, including the cortical hem and the ventral pallium at pallium-subpallium boundary (PSB). CXCR4, the canonical receptor for the chemokine CXCL12, controls the superficial location of hem-derived CR cells. However, recent studies showed that CXCR7, a second CXCL12 receptor, is also expressed in CR cells at early developmental stages. We thus investigated the role of CXCR7 during CR cell development using multiple loss-of-function approaches. Cxcr7 gene inactivation led to aberrant localization of Reelin-positive cells within the pallium. In addition, Cxcr7(-/-) mice were characterized by significant accumulation of ectopic CR cells in the lateral part of the dorsal pallium compared with Cxcr4 knockout mice. Loss-of-function approaches, using either gene targeting or pharmacological receptor inhibition, reveal that CXCR7 and CXCR4 act both in CR positioning. Finally, conditional Cxcr7 deletion in cells derived from Dbx1-expressing progenitors indicates an essential role of CXCR7 in controlling the positioning of a subpopulation of PSB-derived CR cells. Our data demonstrate that CXCR7 has a role in the positioning of hem and PSB-derived CR cells, CXCL12 regulating CR cell subpial localization through the combined action of CXCR4 and CXCR7.

Keywords: Dbx1; Reelin; chemokine receptor; mouse; neocortical development; pallium–subpallium boundary.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Movement*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism
  • Neurons / physiology*
  • Receptors, CXCR / metabolism*
  • Receptors, CXCR4 / metabolism
  • Reelin Protein
  • Serine Endopeptidases / metabolism
  • Signal Transduction


  • CXCR4 protein, mouse
  • Cell Adhesion Molecules, Neuronal
  • Cmkor1 protein, mouse
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Receptors, CXCR
  • Receptors, CXCR4
  • Reelin Protein
  • Reln protein, mouse
  • Serine Endopeptidases