Elucidating the transcriptional mechanisms regulating shear stress mediated gene expression and their role during blood vessel pruning

血管系统由内皮小管的分支网络组成。为了建立这种血管网络，内皮细胞必须协调各种不同的细胞过程。内皮细胞需要响应趋化性信号而迁移、增殖并随后分化。最近的遗传学研究发现了一些参与血管发芽的关键参与者。这些包括VEGF、Notch和G蛋白偶联受体。然而，很少有人知道的空间和时间激活这些途径在一个给定的内皮细胞，以及如何从这些不同的途径输入集成。特别是，我们不明白相邻的血管如何在不对相同的引导线索做出反应的情况下彼此靠近。该研究旨在解决血管生成中的三个基本问题，利用斑马鱼模型系统中体内成像和遗传操作的最新进展。我们将描绘血管形成过程中内皮细胞分裂的贡献，并研究不对称分布的细胞命运决定因素在这一过程中的参与。然后，我们将解决的问题是如何建立区域差异在血管生成萌芽和趋化因子信号如何有助于这一进程。最后，我们将进行一个屏幕，旨在识别新的球员重要的适当血管发芽发生。

The vasculature consists of a ramified network of endothelial tubules. In order to establish this vascular network, endothelial cells must coordinate a variety of different cellular processes. Endothelial cells need to migrate in response to chemotactic cues, proliferate and subsequently differentiate. Recent genetic studies have uncovered a number of key players that are involved in blood vessel sprouting. These include VEGF, Notch and G-protein coupled receptors. However, little is known about the spatial and temporal activation of these pathways within a given endothelial cell and how the inputs from these divergent pathways are integrated. In particular, we do not understand how neighbouring blood vessels navigate in close proximity to one another without responding to the same guidance cues. The proposed research aims to address three fundamental questions in angiogenesis, making use of recent progress in in vivo imaging and genetic manipulations in the zebrafish model system. We will delineate the contribution of endothelial cell divisions during vascular patterning and study the involvement of asymmetrically distributed cell fate determinants in this process. We will then address the question how regional differences are established during angiogenic sprouting and how chemokine signalling contributes to this process. Finally, we will carry out a screen aiming at the identification of new players important for proper blood vessel sprouting to occur.