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Proc Natl Acad Sci U S A. 2001 May 8;98(10):5643-8.

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

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1
Department of Pathology and Obstetrics/Gynecology, Columbia University, 630 West 168th Street, New York, NY 10032, USA.

Abstract

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.

Comment in

PMID:
11344305
PMCID:
PMC33266
DOI:
10.1073/pnas.091584598
[Indexed for MEDLINE]
Free PMC Article

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