title: CXC chemokine receptor 7 (CXCR7) regulates CXCR4 protein expression and capillary tuft development in mouse kidney.
abstract: BACKGROUND
  The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development.
  
  
  RESULTS
  We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping.
  
  
  CONCLUSIONS
  We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries.
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Jena, Friedrich Schiller University Jena, Jena, Germany. sammy.haege@mti.uni-jena.de
authors.forename: Sammy
authors.initials: S
authors.lastname: Haege
authors.forename: Claudia
authors.initials: C
authors.lastname: Einer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Thiele
authors.forename: Wiebke
authors.initials: W
authors.lastname: Mueller
authors.forename: Sandor
authors.initials: S
authors.lastname: Nietzsche
authors.forename: Amelie
authors.initials: A
authors.lastname: Lupp
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Ralf
authors.initials: R
authors.lastname: Stumm
mesh_terms: D000818:Animals; D002196:Capillaries / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000098:blood supply* / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000002:abnormalities / Q000098:blood supply / Q000196:embryology / Q000648:ultrastructure; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009399:Nephrons / Q000196:embryology / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054387:Receptors, CXCR / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D014513:Ureter / Q000196:embryology / Q000378:metabolism
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C501897:Cmkor1 protein, mouse; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D054387:Receptors, CXCR; D019718:Receptors, CXCR4