title: Misregulation of SDF1-CXCR4 signaling impairs early cardiac neural crest cell migration leading to conotruncal defects.
abstract: BACKGROUND
  Cardiac neural crest cells (NCs) contribute to heart morphogenesis by giving rise to a variety of cell types from mesenchyme of the outflow tract, ventricular septum, and semilunar valves to neurons of the cardiac ganglia and smooth muscles of the great arteries. Failure in cardiac NC development results in outflow and ventricular septation defects commonly observed in congenital heart diseases. Cardiac NCs derive from the vagal neural tube, which also gives rise to enteric NCs that colonize the gut; however, so far, molecular mechanisms segregating these 2 populations and driving cardiac NC migration toward the heart have remained elusive.
  
  
  OBJECTIVE
  Stromal-derived factor-1 (SDF1) is a chemokine that mediates oriented migration of multiple embryonic cells and mice deficient for Sdf1 or its receptors, Cxcr4 and Cxcr7, exhibit ventricular septum defects, raising the possibility that SDF1 might selectively drive cardiac NC migration toward the heart via a chemotactic mechanism.
  
  
  RESULTS
  We show in the chick embryo that Sdf1 expression is tightly coordinated with the progression of cardiac NCs expressing Cxcr4. Cxcr4 loss-of-function causes delayed migration and enhanced death of cardiac NCs, whereas Sdf1 misexpression results in their diversion from their normal pathway, indicating that SDF1 acts as a chemoattractant for cardiac NCs. These alterations of SDF1 signaling result in severe cardiovascular defects.
  
  
  CONCLUSIONS
  These data identify Sdf1 and its receptor Cxcr4 as candidate genes responsible for cardiac congenital pathologies in human.
authors.affiliation: Laboratoire de Biologie du Développement, Université Pierre et Marie Curie, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Escot
authors.forename: Cédrine
authors.initials: C
authors.lastname: Blavet
authors.forename: Sonja
authors.initials: S
authors.lastname: Härtle
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Duband
authors.forename: Claire
authors.initials: C
authors.lastname: Fournier-Thibault
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002633:Chemotaxis; D002642:Chick Embryo; D002678:Chimera; D003370:Coturnix / Q000196:embryology; D004475:Ectoderm / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D006345:Heart Septal Defects, Ventricular / Q000235:genetics / Q000503:physiopathology*; D035683:MicroRNAs / Q000235:genetics; D009432:Neural Crest / Q000473:pathology*; D054259:Neural Tube / Q000166:cytology / Q000637:transplantation; D009928:Organ Specificity; D038081:Organogenesis; D054387:Receptors, CXCR / Q000096:biosynthesis / Q000235:genetics; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013045:Species Specificity; D014162:Transfection
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C501897:Cmkor1 protein, mouse; C515256:Cxcl12 protein, mouse; D035683:MicroRNAs; D054387:Receptors, CXCR; D019718:Receptors, CXCR4
keywords: SDF1 chemokine; cardiac development; cardiac neural crest; conotruncal defects genes; heart defects, congenital; migration; receptors, CXCR4