Control of blood vessel development by SOX transcription factors

心血管疾病是澳大利亚最大的健康问题，估计有300万澳大利亚人患有从高血压到心力衰竭的一系列疾病。胚胎中血管发育不正常会影响胚胎的存活，并使患者在出生后易患血管疾病。新血管的生长（血管生成）也是实体瘤在癌症进展期间生长能力的重要因素。因此，了解血管如何形成和再生在健康科学中具有根本的重要性。我们发现了一个基因，Sox 18，它似乎通过控制内皮细胞的形成和/或特性来调节血管的发育，内皮细胞排列在血管上，使其不可渗透。到目前为止，我们的研究表明，SOX 18缺陷的小鼠死于血管缺陷，强调了该基因的重要性。这个项目是关于找出Sox 18如何工作-在缺乏这种基因的小鼠中到底出了什么问题，Sox 18是否可以影响细胞培养中的内皮细胞行为，Sox 18如何在内皮细胞中活跃，Sox 18打开了哪些基因，以及Sox 18在内皮细胞中与哪些基因合作。这些问题的答案将不仅提供有关如何控制血管发育的基本信息，而且还为未来可能的治疗方法播下种子，其中血管发育可以通过药物治疗来刺激（例如伤口愈合）或抑制（例如肿瘤进展）。

Cardiovascular disease is Australia s greatest health problem, with an estimated 3 million Australians suffering a spectrum of conditions from hypertension through to heart failure. Improper development of blood vessels in the embryo can compromise survival of the embryo, and predispose patients to vascular disease after birth. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain an understanding of how blood vessels form and regenerate. We discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the formation and-or properties of endothelial cells, which line the blood vessels and make them impermeable. Our research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS, underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to these questions will not only provide fundamental basic information about how blood vessels development is controlled, but also sow the seeds for possible future therapies in which blood vessel development could be stimulated (eg in wound healing) or suppressed (eg in tumour progression) by drug treatments.