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Blood, 5 November 2009, Vol. 114, No. 19, pp. 4300-4309. Prepublished online as a Blood First Edition Paper on September 9, 2009; DOI 10.1182/blood-2008-12-193326. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-12-193326v1 114/19/4300    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Zhang, B. Articles by Wang, L. PubMed PubMed Citation Articles by Zhang, B. Articles by Wang, L. Related Collections Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Repulsive axon guidance molecule Slit3 is a novel angiogenic factor Bing Zhang1, Ursula M. Dietrich2, Jian-Guo Geng3, Roy Bicknell4, Jeffrey D. Esko5, and Lianchun Wang1 1 Complex Carbohydrate Research Center, Department of Biochemistry and Molecular Biology, University of Georgia, Athens; 2 Department of Small Animal Medicine & Surgery, College of Veterinary Medicine, University of Georgia, Athens; 3 Vascular Biology Center, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis; 4 Cancer Research UK Angiogenesis Group, Institute for Biomedical Research, University of Birmingham Medical School, Edgbaston, United Kingdom; and 5 Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California San Diego, La Jolla Slits are large, secreted repulsive axon guidance molecules. Recent genetic studies revealed that the Slit3 is dispensable for neural development but required for non-neuron–related developmental processes, such as the genesis of the diaphragm and kidney. Here we report that Slit3 potently promotes angiogenesis, a process essential for proper organogenesis during embryonic development. We observed that Slit3 is expressed and secreted by both endothelial cells and vascular smooth muscle cells in vasculature and that the Slit cognate receptors Robo1 and Robo4 are universally expressed by endothelial cells, suggesting that Slit3 may act in paracrine and autocrine manners to regulate endothelial cells. Cellular function studies revealed that Slit3 stimulates endothelial-cell proliferation, promotes endothelial-cell motility and chemotaxis via interaction with Robo4, and accelerates endothelial-cell vascular network formation in vitro with a specific activity comparable with vascular endothelial growth factor. Furthermore, Slit3 stimulates neovessel sprouting ex vivo and new blood vessel growth in vivo. Consistent with these observations, the Slit3 knockout mice display disrupted angiogenesis during embryogenesis. Taken together, our studies reveal that the repulsive axon guidance molecule Slit3 is a novel and potent angiogenic factor and functions to promote angiogenesis in coordinating organogenesis during embryonic development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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