Slit/Robo signalling in cardiomyocyte cytokinesis

While improved access and advances in early therapeutic interventions have led to a significant reduction in the rate of death immediately after heart attacks, the chronic consequences remain a major health concern. The adult heart lacks the capability to replace damaged tissue with new cardiac muscle, leading to long-term functional impairment, progressive cardiac failure and often eventually death. Interestingly, new-born mice can create new heart muscle cells (cardiomyocytes) and functional cardiac muscle after injury, but this reparative potential is short-lived. Cardiomyocytes lose their ability to divide (undergo cytokinesis) soon after birth, thus preventing the heart from recovering after damage.

Proteins in the space between cells can alter the behaviour of cells in their vicinity. Recent work found that the composition of these protein mixtures changes soon after birth. One protein that disappears from the mixture is called Slit2 and can promote the division of heart muscle cells. Slit2 is not only found between cells, but also inside cells. This project will investigate the importance of Slit2 inside cardiomyocytes for their division and test if treatment with Slit2 can improve heart repair after injury.

Image title: To divide or not to divide - EdU-labelled mono- and binuclear cardiomyocytes

© Dr Susann Bruche