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Publication : Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium.

First Author  Uyttendaele H Year  2001
Journal  Proc Natl Acad Sci U S A Volume  98
Issue  10 Pages  5643-8
PubMed ID  11344305 Mgi Jnum  J:69406
Mgi Id  MGI:1934537 Doi  10.1073/pnas.091584598
Citation  Uyttendaele H, et al. (2001) Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium. Proc Natl Acad Sci U S A 98(10):5643-8
abstractText  Notch proteins function as receptors for membrane-bound ligands (Jagged and Delta-like) to regulate cell-fate determination. We have investigated the role of Notch signaling in embryonic endothelium of the mouse by expressing an activated form of the Notch4 protein in vasculature under the regulation of the Flk1 (VEGFR) locus. Expression of activated Notch4 results in a growth and developmental delay and embryonic lethality at about 10 days postcoitum. The extent of the developing vasculature in mutant embryos was restricted, fewer small vessels were seen, and vascular networks were disorganized. The brain periphery of mutant embryos contained large dilated vessels with evidence of compromised vessel-wall integrity and large areas of necrosis; yolk-sac vasculature was abnormal. Expression of an activated form of Notch4 in embryonic vasculature leads to abnormal vessel structure and patterning, implicating the Notch pathway in phases of vascular development associated with vessel patterning and remodeling.
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