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，动脉和静脉的形成。这两种血管类型之间的差异是由于发育早期的替代分子信号而产生的。然而，人们对这些信号以及静脉特异性基因如何在静脉中打开和在动脉中关闭知之甚少。了解这一过程对于理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，静脉经常被用来替换受损的动脉，但通常不能正确地适应，而动脉-静脉分化缺陷可能导致血管扩大，有灾难性破裂的风险。这些增强子区域通过与称为转录因子的蛋白质结合来控制基因的开启或关闭。我们发现了两种可以专门在静脉中开启基因的增强子。该项目旨在发现哪些转录因子结合并控制这些静脉特异性增强子，并了解哪些外部信号导致这种情况发生。我们还将使用这些基因开关来制作一种动物模型，该模型能够专门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.