%0 Journal Article
%T Notch signaling regulates remodeling and vessel diameter in the extraembryonic yolk sac
%A Jessica N Copeland
%A Yi Feng
%A Naveen K Neradugomma
%A Patrick E Fields
%A Jay L Vivian
%J BMC Developmental Biology
%D 2011
%I BioMed Central
%R 10.1186/1471-213x-11-12
%X Conditional transgenic models were used to expand and ablate Notch signaling in the early embryonic endothelium. Embryos with activated Notch1 signaling in the vasculature displayed a variety of defects, and died soon after E10.5. Most notably, the extraembryonic vasculature of the yolk sac displayed remodeling differentiation defects, with greatly enlarged lumens. These phenotypes were distinct from endothelial loss-of-function of RBPJ, a transcriptional regulator of Notch activity. Gene expression analysis of RNA isolated from the yolk sac endothelia of transgenic embryos indicated aberrant expression in a variety of genes in these models. In particular, a variety of secreted factors, including VEGF and TGF-¦Â family members, displayed coordinate expression defects in the loss-of-function and gain-of-function models.Morphological analyses of the in vivo models confirm and expand the understanding of Notch signaling in directing endothelial development, specifically in the regulation of vessel diameter in the intra- and extraembryonic vasculature. Expression analysis of these in vivo models suggests that the vascular differentiation defects may be due to the regulation of key genes through the Notch-RBPJ signaling axis. A number of these genes regulated by Notch signaling encode secreted factors, suggesting that Notch signaling may mediate remodeling and vessel diameter in the extraembryonic yolk sac via autocrine and paracrine cell communication. We propose a role for Notch signaling in elaborating the microenvironment of the nascent arteriole, suggesting novel regulatory connections between Notch signaling and other signaling pathways during endothelial differentiation.The formation of the vascular system is essential for nutrient and waste transport in the growing embryo. In mice, the developing vasculature initially forms in intraembryonic and extraembryonic regions. In the extraembryonic yolk sac at approximately E7.0-7.5, angioblasts are formed from the differ
%U http://www.biomedcentral.com/1471-213X/11/12