title: CXCL12 Signaling Is Essential for Maturation of the Ventricular Coronary Endothelial Plexus and Establishment of Functional Coronary Circulation.
abstract: Maturation of a vascular plexus is a critical and yet incompletely understood process in organ development, and known maturation factors act universally in all vascular beds. In this study, we show that CXCL12 is an organ-specific maturation factor of particular relevance in coronary arterial vasculature. In vitro, CXCL12 does not influence nascent vessel formation, but promotes higher-order complexity of preinitiated vessels. In the heart, CXCL12 is expressed principally by the epicardium, and its receptor CXCR4 is expressed by coronary endothelial cells. CXCL12 is not a chemotactic signal for endothelial cell migration, but rather acts in a paracrine manner to influence the maturation of the coronary vascular plexus. Mutants in CXCL12 signaling show an excess of immature capillary chains and a selective failure in arterial maturation, and become leaky with the onset of coronary perfusion. Failed maturation of the coronary system explains the late-gestation lethality of these mutants.
authors.affiliation: Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: ccavalle@usc.edu.
authors.forename: Susana
authors.initials: S
authors.lastname: Cavallero
authors.affiliation: Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Yi
authors.affiliation: Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Saban Research Institute of Children's Hospital, Los Angeles, CA 90027, USA.
authors.forename: Ching-Ling
authors.initials: CL
authors.lastname: Lien
authors.affiliation: Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: S Ram
authors.initials: SR
authors.lastname: Kumar
authors.affiliation: Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: sucov@usc.edu.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Sucov
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000166:cytology / Q000196:embryology*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D005337:Fibrin