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Overexpression of delta-like 4 induces arterialization and attenuates

dc.contributor.authorTrindade, A.
dc.contributor.authorKumar, S.R.
dc.contributor.authorScehnet, J.S.
dc.contributor.authorLopes-da-Costa, L.
dc.contributor.authorBecker, J.D.
dc.date.accessioned2010-03-18T12:08:38Z
dc.date.available2010-03-18T12:08:38Z
dc.date.issued2008-09
dc.description.abstractThe 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.pt
dc.identifier.citationTrindade, Alexandre, Kumar, S. Ram, Scehnet, Jeffrey S, Lopes-da-Costa, Luis, Bekcher, Jorg, wiedong (2008). Overexpression of delta-like 4 induces arterialization and attenuates. Blood. 112: 1720-1729pt
dc.identifier.issn0006-4971
dc.identifier.urihttp://hdl.handle.net/10400.7/69
dc.identifier.urihttp://dx.doi.org/10.1182/blood-2007-09-112748
dc.language.isoengpt
dc.publisherAmerican Society of Hematologypt
dc.subjectIntracellular Signaling Peptides and Proteins/genetics/physiologypt
dc.subjectMembrane Proteins/genetics/physiologypt
dc.subjectNeovascularization, Physiologic/genetics/physiologypt
dc.titleOverexpression of delta-like 4 induces arterialization and attenuatespt
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1729pt
oaire.citation.startPage1720pt
oaire.citation.titleBloodpt
rcaap.rightsopenAccesspt
rcaap.typearticlept

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