Effect of endothelial depletion of Wt1 on gene expression during coronary plexus sprouting in the heart

Coronary blood vessel formation is a highly regulated process in which endothelial cells (ECs) play an essential role. During the last years, new pieces of evidence have demonstrated WT1 expression in coronary ECs. However, its role in coronary blood vessel formation was almost unknown. Here we generated an inducible endothelial-specific Wt1KO mouse model (Wt1KOΔEC). The analysis of these mutant mice has demonstrated that deletion of Wt1 in coronary ECs impairs coronary blood vessels and myocardium development. The transcriptomic analysis of coronary ECs from Wt1KOΔEC mice demonstrated that deletion of Wt1 has a great impact on the molecular signature of coronary ECs that correlate with defects in cell proliferation, migration, and differentiation. These results provide novel insights into the role of WT1 in heart development and demonstrate that WT1 in ECs is required for coronary blood vessel formation. To investigate the role of WT1 in coronary endothelial cells from the coronary plexus during initial stages of sprouting angiogenesis of the heart, we generated an inducible endothelial-specific Wt1KO mouse model (Wt1KOΔEC) in which both lineage tracing expression of membrane GFP (mGFP) and deletion of Wt1 is induced upon tamoxifen administration. We administered pregnant mice during E11.5-13.5 stages, isolated embryo hearts at E15.5 and FACS-sorted mGFP+ cells. We then performed gene expression profiling analysis using data obtained from RNA-seq of ControlΔEC (n=3) and Wt1KOΔEC (n=3) coronary endothelial cells