Wt1 Gene Found to Affect Myocardial Development in Mice

Scientists from the University of Barcelona (UB) recently found that endothelial cells play an essential role in the development of the mammalian heart, particularly during the early stages of coronary vessel formation. The study, published in Development and led by Professor Ofelia Martínez-Estrada, suggests that deletion of the Wt1 gene in endothelial cells results in incorrect heart development during embryonic stages.

Endothelial cells help transport nutrients and metabolites to and from underlying tissues and have a range of essential functions in tissue and organ development. The Wt1 gene is highly expressed in the epicardium, the heart’s outer layer, and endothelial cells (ECs). 

The study utilized image analysis and RNA-Seq techniques on knockout mouse models (Wt1KOΔEC) to see how Wt1 deletion modifies these cell types’ transcriptional signatures, which correlate with defects in the formation and differentiation of arteries and veins, as well as with a decrease in cardiomyocyte proliferation, which are crucial for proper embryonic heart development.

RNA-Seq analysis of coronary ECs from Wt1KOΔEC mice demonstrated Wt1 deletion significantly impacted the molecular signatures of coronary ECs and modified the expression of several genes modulated throughout coronary EC development. Many of these differentially expressed genes are involved in cell proliferation, migration and differentiation of coronary ECs; consequently, these were the same processes seen to be affected in Wt1KOΔEC mice.

While previous research suggested that alterations in embryonic heart formation observed in Wt1KO transgenic mouse models were mainly due to this gene’s function in the epicardium, the new study shows that deletion of the Wt1 gene in ECs directly affects coronary vessel formation and myocardial development.

The team’s results provide insight into endothelial cells’ role in coronary vessel formation and highlight the importance of further research into the role of the Wt1 gene in the revascularisation processes of ischaemic hearts.