Revealing the role of two proteins in congenital defects of the circulation

The role of CAS family members BCAR1/p130Cas and NEDD9 in angiogenesis

The circulation system develops in the unborn baby in the earliest weeks and months of life. The human body has three main types of vessels: arteries that transport oxygenated blood from the heart to the organs, veins to carry poorly-oxygenated blood back to the heart, and lymphatic vessels responsible for removing excess of fluid from tissue. The distinction between making arteries and veins (a process called angiogenesis) or lymphatic vessels (lymphangiogenesis) is one of the earliest and most important events of vessel development, and can lead to birth defects when it goes wrong. Work from Dr Paul Frankel and other groups has identified two proteins, called p130Cas and Nedd9, as important in normal and abnormal angiogenesis and lymphangiogenesis. They have shown in zebrafish that the loss of p130Cas leads to defects in vein and lymph vessel formation. In this project, they will further explore the mechanisms driven by p130Cas and Nedd9 to specifically make arteries, veins or lymph vessels. This will increase our understanding of the molecular mechanisms involved in circulatory defects in babies and may offer clues to how we might prevent them.