Author:
Uyttendaele H.,Ho J.,Rossant J.,Kitajewski J.
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.
Publisher
Proceedings of the National Academy of Sciences
Cited by
269 articles.
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