Regulatory pathways controlling venous identity

哺乳动物的循环系统依赖于两种不同类型的血管的形成，即动脉和静脉。这两种血管类型之间的差异是由于发育早期不同的分子信号引起的。然而，人们对这些信号以及静脉特有基因如何在静脉中开启和在动脉中关闭知之甚少。了解这一过程对于了解和治疗心血管疾病至关重要。例如，在冠状动脉搭桥手术中，静脉经常被用来取代受损的动脉，但往往不能正确适应，动静脉分化缺陷可能导致血管扩大，有灾难性破裂的风险。这项研究将研究被称为增强子的DNA区域。这些增强子区域通过结合被称为转录因子的蛋白质来控制基因的开启或关闭。我们已经发现了两种增强剂，它们可以专门在静脉中开启基因。这个项目的目的是找出哪些转录因子结合并控制这些血管特异性增强子，并了解是什么外部信号导致了这种情况的发生。我们还将使用这些基因开关来制作一种动物模型，能够从静脉中删除任何感兴趣的基因。

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.