Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants.

Abstract:

:The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand exhibit haploinsufficient lethality because of defects in vascular remodeling. We also describe vascular defects in embryos homozygous for a mutation in the Rbpsuh gene, which encodes the primary transcriptional mediator of Notch signaling. Conditional inactivation of Rpbsuh function demonstrates that Notch activation is essential in the endothelial cell lineage. Notch pathway mutant embryos exhibit defects in arterial specification of nascent blood vessels and develop arteriovenous malformations. These results demonstrate that vascular remodeling in the mouse embryo is sensitive to Dll4 gene dosage and that Notch activation in endothelial cells is essential for embryonic vascular remodeling.

journal_name

Genes Dev

journal_title

Genes & development

authors

Krebs LT,Shutter JR,Tanigaki K,Honjo T,Stark KL,Gridley T

doi

10.1101/gad.1239204

subject

Has Abstract

pub_date

2004-10-15 00:00:00

pages

2469-73

issue

20

eissn

0890-9369

issn

1549-5477

pii

gad.1239204

journal_volume

18

pub_type

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