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Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7.

Chemotactic cytokines (chemokines) attract immune cells, although their original evolutionary role may relate more closely with embryonic development. We noted differential expression of the chemokine receptor CXCR7 (RDC-1) on marginal zone B cells, a cell type associated with autoimmune diseases. We generated Cxcr7(-/-) mice but found that CXCR7 deficiency had little effect on B cell composition. However, most Cxcr7(-/-) mice died at birth with ventricular septal defects and semilunar heart valve malformation. Conditional deletion of Cxcr7 in endothelium, using Tie2-Cre transgenic mice, recapitulated this phenotype. Gene profiling of Cxcr7(-/-) heart valve leaflets revealed a defect in the expression of factors essential for valve formation, vessel protection, or endothelial cell growth and survival. We confirmed that the principal chemokine ligand for CXCR7 was CXCL12/SDF-1, which also binds CXCR4. CXCL12 did not induce signaling through CXCR7; however, CXCR7 formed functional heterodimers with CXCR4 and enhanced CXCL12-induced signaling. Our results reveal a specialized role for CXCR7 in endothelial biology and valve development and highlight the distinct developmental role of evolutionary conserved chemokine receptors such as CXCR7 and CXCR4.

Pubmed ID: 17804806


  • Sierro F
  • Biben C
  • Martínez-Muñoz L
  • Mellado M
  • Ransohoff RM
  • Li M
  • Woehl B
  • Leung H
  • Groom J
  • Batten M
  • Harvey RP
  • Martínez-A C
  • Mackay CR
  • Mackay F


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

September 11, 2007

Associated Grants

  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Animals
  • Chemokine CXCL12
  • Chemokines, CXC
  • Fluorescence Recovery After Photobleaching
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Heart
  • Heart Valves
  • Hematopoiesis
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Morphogenesis
  • Protein Binding
  • Receptors, CXCR
  • Receptors, G-Protein-Coupled