WT1 is a transcription factor expressed in the heart epicardium (the outermost layer of the heart) and is required for epicardial development, with Wt1 knockout mice displaying cardiovascular defects and embryonic lethality. Although WT1 is also expressed in coronary endothelial cells (ECs), little was known about its role in these cells and its contribution to blood vessel formation. Now, Ofelia Martinez-Estrada and colleagues develop an inducible knockout mouse line (Wt1KOΔEC) to specifically knockout Wt1 in Pdgfb-expressing coronary ECs starting between E11.5 and E13.5. The authors show that Wt1KOΔEC mice have impaired coronary blood vessel and myocardium (heart muscle) development, caused by a reduction in proliferating cardiomyocytes and ECs. To understand these defects, the researchers transcriptionally profile Wt1KOΔEC coronary ECs and reveal that WT1 is a major regulator of their transcriptome, with mutant ECs failing to upregulate key maturation genes. In addition, using immunostaining, image analysis and in vitro approaches, they show that deletion of Wt1 impairs coronary EC proliferation, migration and maturation. Loss of Wt1 also affects the differentiation into venous and arterial ECs in early coronary plexus formation and coronary artery formation in later development. Together, these data demonstrate that WT1 is crucial for coronary EC development.
