Finding out what controls the location of nerves in the heart

Exploring the role of Slit-Robo signalling in cardiac innervation

Dr Mathilda Mommersteeg is studying how the nervous system is involved in heart and circulatory disease, and what controls the location of nerves within the heart. Although the heart beats on its own, the heart’s nerve supply helps to alter the frequency and pumping force of the heartbeat, for instance during exercise. Nerve abnormalities can result in heart rhythm disturbances (arrhythmias). This can also happen after a heart attack, when part of the heart muscle has died and is replaced by scar tissue. Here, nerves supplying the heart can grow back into the scar area incorrectly and can stimulate the wrong cells to start beating, resulting in abnormal heart rhythms. We do not yet understand what determines the positioning of nerves in the heart during development and in disease. In this project, Dr Mommersteeg will work out how a signalling pathway called Slit-Robo governs where nerves are located in the heart. She will find out what signals the Slit-Robo pathway sends to nerves to either enter or avoid certain regions of the heart when the nerves are first formed, and what happens if these signals are absent. This study, in mice, will help us understand what guides nerve location in the developing heart and why nerves can wrongly regrow into regions during heart disease. It may reveal new ways to manipulate nerves to prevent and treat abnormal heart rhythms.