Regulatory pathways controlling venous identity

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The circulatory system of mammals is dependent on the formation of two distinct types of blood vessel, arteries and veins. The differences between these two blood vessel types arise due to alternative molecular signals early on in development. However, very little is known about these signals and how vein-specific genes are switched on in veins and off in arteries. Understanding this process is crucial for understanding and treating cardiovascular disease. For example, veins are often used to replace damaged arteries in coronary bypass surgery but often do not correctly adapt, and defective arterial-venous differentiation can lead to enlarged blood vessels at risk of catastrophic ruptures.This study will look at regions of DNA called enhancers. These enhancer regions control whether a gene is on or off through the binding of proteins called transcription factors. We have found two enhancers which can switch genes on specifically in veins. This project aims to find what transcription factors bind to, and control, these vein-specific enhancers, and to understand what external signals cause this to happen. We will also use these gene switches to make an animal model capable of deleting any gene of interest specifically from veins.