Investigating transcriptional networks controlled by Wilms’ tumour 1 in the developing heart

A heart attack occurs when blood flow to a large portion of the heart decreases or stops, causing damage to the heart muscle. Nearly one billion of muscle cells are permanently lost after such event and replaced by non-contractile scar tissue in a process called fibrosis that further compromises the function of the heart and ultimately, leads to heart failure. To date, no treatment has been effective in mending the heart following a heart attack. Our recent work has shown that the heart attempts to replenish its damaged tissue, by reverting to similar processes that were used in the embryo to build the heart before birth. In particular, cells from the outer layer of the heart, the epicardium, become activated in a process called epithelial-to-mesenchymal transition (EMT), but this activation is transient and insufficient to support new blood vessel and muscle growth as it happens in the embryo. Of importance, epicardial cell fate decisions during EMT are directed by sequence-specific DNA-binding factors, such as the transcription factor Wilms’ tumour 1 (WT1), but its function remains poorly understood. Thus, we propose that understanding the process of EMT in greater detail, with a specific focus on WT1, will enable the development of better drugs to stimulate the heart to repair itself more efficiently after a heart attack. The award from the Oxford BHF Centre of Research Excellence will support this research.

 © Dr Joaquim Miguel Vieira

Title: WT1-mediated (pro-)epicardial EMT in the developing mouse embryo

Image credit: Dr Joaquim Miguel Vieira

Description: WT1-expressing cells (red) undergo EMT, delaminating from the proepicardium, a transient structure at the base of the inflow tract (sinus venosus) of the heart, and attached to the ventricular wall forming the outer layer of the heart, the epicardium. Green, smooth muscle actin-alpha; Blue, DAPI staining of the cell nucleus.