Notch regulates multiple signaling pathways during extra‐embryonic vascular differentiation of the yolk sac

The signaling cascades that direct the morphological differentiation of the vascular system during early embryogenesis are not well defined. To further understand the role of Notch signaling during endothelial differentiation, we are using both gain‐of‐function and loss‐of‐function approaches in vivo. Embryos with activated Notch signaling in the vasculature display a variety of defects, and die soon after E10.5. Most notably, the extra‐embryonic vasculature of the yolk sac displays remodeling differentiation defects, with few matured vessels. Gene expression analysis of RNA isolated from the yolk sac of transgenic embryos indicates aberrant expression in a variety of genes in Notch signaling gain‐of‐function and loss‐of‐function models. In particular, VEGF and TGF‐beta family members show coordinated expression defects in these models. This data suggests potential regulatory connections between Notch signaling and other signaling pathways during endothelial differentiation. Based on these findings, we are exploring other transgenic and embryo culture models to further understand the relevance of the misexpression of VEGF‐ and TGF‐beta‐related signaling in these in vivo models. Completion of this work will provide information on cell signals and gene expression changes that direct endothelial differentiation. Support for this research is provided by AHA Predoctoral Fellowship from JNC.