title: Peripheral nerve-derived CXCL12 and VEGF-A regulate the patterning of arterial vessel branching in developing limb skin.
abstract: In developing limb skin, peripheral nerves provide a spatial template that controls the branching pattern and differentiation of arteries. Our previous studies indicate that nerve-derived VEGF-A is required for arterial differentiation but not for nerve-vessel alignment. In this study, we demonstrate that nerve-vessel alignment depends on the activity of Cxcl12-Cxcr4 chemokine signaling. Genetic inactivation of Cxcl12-Cxcr4 signaling perturbs nerve-vessel alignment and abolishes arteriogenesis. Further in vitro assays allow us to uncouple nerve-vessel alignment and arteriogenesis, revealing that nerve-derived Cxcl12 stimulates endothelial cell migration, whereas nerve-derived VEGF-A is responsible for arterial differentiation. These findings suggest a coordinated sequential action in which nerve Cxcl12 functions over a distance to recruit vessels to align with nerves, and subsequent arterial differentiation presumably requires a local action of nerve VEGF-A in the nerve-associated vessels.
authors: Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10/6C103, 10 Center Drive, Bethesda, MD 20892, USA.
authors: Wenling
authors: W
authors: Li
authors: Hiroshi
authors: H
authors: Kohara
authors: Yutaka
authors: Y
authors: Uchida
authors: Jennifer M
authors: JM
authors: James
authors: Kosha
authors: K
authors: Soneji
authors: Darran G
authors: DG
authors: Cronshaw
authors: Yong-Rui
authors: YR
authors: Zou
authors: Takashi
authors: T
authors: Nagasawa
authors: Yoh-Suke
authors: YS
authors: Mukouyama
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005121:Extremities / Q000196:embryology*; D005434:Flow Cytometry; D005727:Ganglia, Spinal / Q000378:metabolism*; D017403:In Situ Hybridization; D019426:Integrases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000196:embryology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C045073:Cre recombinase; D019426:Integrases
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