Abstract
Mouse embryos lacking the polycomb group gene member Yin-Yang1 (YY1) die during the peri-implantation stage. To assess the post-gastrulation role of YY1, a conditional knock-out (cKO) strategy was used to delete YY1 from the visceral endoderm of the yolk sac and the definitive endoderm of the embryo. cKO embryos display profound yolk sac defects at 9.5 days post coitum (dpc), including disrupted angiogenesis in mesoderm derivatives and altered epithelial characteristics in the visceral endoderm. Significant changes in both cell death and proliferation were confined to the YY1-expressing yolk sac mesoderm indicating that loss of YY1 in the visceral endoderm causes defects in the adjacent yolk sac mesoderm. Production of Vascular Endothelial Growth Factor A (VEGFA) by the visceral endoderm is essential for normal growth and development of the yolk sac vasculature. Reduced levels of VEGFA are observed in the cKO yolk sac, suggesting a cause for the angiogenesis defects. Ex vivo culture with exogenous VEGF not only rescued angiogenesis and apoptosis in the cKO yolk sac mesoderm, but also restored the epithelial defects observed in the cKO visceral endoderm. Intriguingly, blocking the activity of the mesoderm-localized VEGF receptor, FLK1, recapitulates both the mesoderm and visceral endoderm defects observed in the cKO yolk sac. Taken together, these results demonstrate that YY1 is responsible for maintaining VEGF in the developing visceral endoderm and that a VEGF-responsive paracrine signal, originating in the yolk sac mesoderm, is required to promote normal visceral endoderm development.
Highlights
Yin-Yang 1 (YY1) is aptly named because of its documented roles as a transcriptional activator and repressor, binding directly to DNA via a consensus-binding site or as part of repressive complexes
At 9.0 dpc, blood flow in the conditional knock-out (cKO) yolk sac is indistinguishable from that of WT, flow is impeded in the cKO yolk sacs at 9.5 dpc, coincident with the observed vascular defects
While YY1 is not required for embryonic endoderm-derived organ specification, we find that YY1 is essential in the visceral endoderm to support angiogenesis in the adjacent mesoderm
Summary
Yin-Yang 1 (YY1) is aptly named because of its documented roles as a transcriptional activator and repressor, binding directly to DNA via a consensus-binding site or as part of repressive complexes. In vitro analysis has revealed that YY1 is required for appropriate regulation of a variety of basic cellular processes including proliferation, cytokinesis, epithelial-mesenchymal transition, apoptosis and DNA repair [1]. Based on these diverse roles in essential cellular processes in normal cells it is not surprising that inappropriate regulation of Yy1 is believed to influence oncogenesis [2,3]. YY1 is the vertebrate homolog of the Drosophila pleiohomeotic (Pho), a member of the polycomb group (PcG) of proteins. Pho is an essential member of the multiprotein Polycomb Repressive Complex, providing DNA binding activity [4]. YY1 has been shown to interact with vertebrate PRC2 complex members it remains unclear if YY1 targets PRC2 in mammalian cells [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
