WT1 in Cardiac Development and Disease

ABSTRACT

The heart is essential for realizing the distribution of oxygen and nutrients throughout the body. Therefore, the heart is the first organ to develop and is already functional in its most primitive structure during embryogenesis. Recent studies indicate that the transcription factor Wilms’ tumor-1 (WT1) is important for many aspects of cardiac development. WT1 expression is first observed in the proepicardium, a group of progenitor cells that give rise to a mesothelial sheet covering the heart, the epicardium. WT1 expression in epicardial cells is required for their epithelial-to-mesenchymal transformation forming epicardium-derived cells that will contribute to the formation of coronary vessels and interstitial fibroblasts. Endothelial cells within the heart also express WT1, whereas the endothelial cells in other parts of the embryo do not. The endothelial expression of WT1 during cardiac development is likely to be important for vascular formation. After cardiac injury, WT1 is temporally upregulated in the epicardium and in the endothelial cells in the infarcted area and border zone, which points to a potential important role for WT1 in cardiac repair and regeneration. In this chapter, we describe the many faces of WT1 within the heart.