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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1720-1729. Prepublished online as a Blood First Edition Paper on June 17, 2008; DOI 10.1182/blood-2007-09-112748. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-09-112748v1 112/5/1720    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Trindade, A. Articles by Duarte, A. Search for Related Content PubMed PubMed Citation Articles by Trindade, A. Articles by Duarte, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Overexpression of delta-like 4 induces arterialization and attenuates vessel formation in developing mouse embryos Alexandre Trindade1,2, S. Ram Kumar3,4, Jeffrey S. Scehnet3, Luis Lopes-da-Costa1, Jorg Becker2, Weidong Jiang5, Ren Liu5, Parkash S. Gill3,6, and Antonio Duarte1,2 1 Centro de Informatica do Instituto Superior de Agronomia (CIISA), Lisbon Technical University, Lisbon, Portugal; 2 Instituto Gulbenkian de Ciência, Oeiras, Portugal; Departments of3 Pathology and, 4 Surgery, University of Southern California Keck School of Medicine, Los Angeles; 5 Vasgene Therapeutics, Los Angeles, CA; and 6 Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles The importance of Notch signaling pathway in the regulation of vascular development and angiogenesis is suggested by the expression of Notch receptors and ligands in vascular endothelial cells (ECs) and the observed vascular phenotypes in mutants of Notch receptors or ligands, especially Dll4. DLL4 is specifically expressed in arterial ECs during development, and haplo-insufficiency is embryonically lethal in mice. To address the role of Dll4 in vascular development, we produced mDll4 conditionally overexpressed transgenic mice that were crossed with constitutive recombinase cre lines. Double transgenic embryos displayed grossly enlarged dorsal aortae (DA) and died before embryonic day 10.5 (E10.5), showing a variable degree of premature arteriovenous fusion. Veins displayed ectopic expression of arterial markers. Other defects included reduced vascular sprouting, EC proliferation, and migration. mDll4 overexpression also inhibited VEGF signaling and increased fibronectin accumulation around the vessels. In vitro and in vivo studies of DLL4-FL (Dll4–full-length) in ECs recapitulate many of the mDll4 transgenics findings, including decreased tube formation, reduced vascular branching, fewer vessels, increased pericyte recruitment, and increased fibronectin expression. These results establish the role of Dll4 in arterial identity determination, and regulation of angiogenesis subject to dose and location. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Skuli, L. Liu, A. Runge, T. Wang, L. Yuan, S. Patel, L. Iruela-Arispe, M. C. Simon, and B. Keith Endothelial deletion of hypoxia-inducible factor-2{alpha} (HIF-2{alpha}) alters vascular function and tumor angiogenesis Blood, July 9, 2009; 114(2): 469 - 477. [Abstract] [Full Text] [PDF]

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