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

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

  • Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14759-64. doi: 10.1073/pnas.0702229104.
Frederic Sierro 1,  Christine Biben,  Laura Martínez-Muñoz,  Mario Mellado,  Richard M Ransohoff,  Meizhang Li,  Blanche Woehl,  Helen Leung,  Joanna Groom,  Marcel Batten,  Richard P Harvey,  Carlos Martínez-A,  Charles R Mackay,  Fabienne Mackay
Affiliations

Affiliation

  • 1 Department of Immunology and Inflammation, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst NSW 2010, Australia.
PMID: 17804806 DOI: 10.1073/pnas.0702229104
Abstract

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.

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