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Blood, 28 May 2009, Vol. 113, No. 22, pp. 5680-5688. Prepublished online as a Blood First Edition Paper on January 14, 2009; DOI 10.1182/blood-2008-08-174508. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-08-174508v1 113/22/5680    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 Sörensen, I. Articles by Gossler, A. PubMed PubMed Citation Articles by Sörensen, I. Articles by Gossler, A. Related Collections Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries Inga Sörensen1, Ralf H. Adams2,3, and Achim Gossler1 1 Institute for Molecular Biology, Medizinische Hochschule Hannover, Hannover; 2 Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Münster; and 3 Faculty of Medicine, University of Münster, Münster, Germany Notch signaling has been shown to regulate various aspects of vascular development. However, a specific role of the ligand Delta-like 1 (DLL1) has not been shown thus far. Here, we demonstrate that during fetal development, DLL1 is an essential Notch ligand in the vascular endothelium of large arteries to activate Notch1 and maintain arterial identity. DLL1 was detected in fetal arterial endothelial cells beginning at embryonic day 13.5. While DLL4-mediated activation has been shown to suppress vascular endothelial growth factor (VEGF) pathway components in growing capillary beds, DLL1-Notch signaling was required for VEGF receptor expression in fetal arteries. In the absence of DLL1 function, VEGF receptor 2 (VEGFR2) and its coreceptor, neuropilin-1 (NRP1), were down-regulatedin mutant arteries, which was followed by up-regulation of chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), a repressor of arterial differentiation and Nrp1 expression in veins. Consistent with a positive modulation of the VEGF pathway by DLL1, the Nrp1 promoter contains several recombinant signal-binding protein 1 for J (RBPJ)–binding sites and was responsive to Notch activity in cell culture. Our results establish DLL1 as a critical endothelial Notch ligand required for maintaining arterial identity during mouse fetal development and suggest context-dependent interrelations of the VEGFA and Notch signaling pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Dll1 and Dll4: similar, but not the same Manfred Gessler Blood 2009 113: 5375-5376. [Full Text] [PDF]

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