Answering fundamental questions about heart development

Tbx1 and cardiovascular morphogenesis: genetic networks and tissue interactions (renewal: years 11-15)

Abnormalities in the heart and circulatory system (often called congenital heart disease) are the commonest defects that can be present at birth. Unlocking the genetic secrets behind how the heart develops in the growing embryo may not only benefit treatment and prevention of birth defects, but also has a much wider application in the development of strategies to regenerate heart tissue in adults with heart failure. Scientists understand that most defects in heart development are caused by abnormalities in certain genes, some of which influence the movement of cells in the developing embryo. These genes are important in forming organs, other tissues and limbs. However, many of the specific genes responsible have yet to be identified. Through pioneering research – some of which was funded by the BHF – Professor Peter Scambler at the Institute of Child Health in London pinned down the exact gene that causes a condition called DiGeorge syndrome. Three-quarters of patients with this disease have an abnormality in the heart, and the chance of death in early infancy is very high. The gene, called Tbx1, is disrupted during development of the embryo in the womb. In this five year programme, he is looking at why Tbx1 is so important for correct development of the heart and vessels. The research will lead to greater understanding of how the embryo develops, which could in the future be used in treatments to regrow and repair heart muscle damaged by disease. Professor Scambler will now investigate what happens when Tbx1 is not produced in mice and chick embryos, and the knock-on effects this has on the action of other genes that are important during embryonic development. Using a special dye, he will follow the activity of Tbx1 to look specifically at how it drives the growth and movement of cells that make up the heart and circulatory system.