Goishi Katsutoshi, Klagsbrun Michael
Vascular Biology Program, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Curr Top Dev Biol. 2004;62:127-52. doi: 10.1016/S0070-2153(04)62005-9.
There is intense interest in how blood vessel development is regulated. A number of vascular growth factors and their receptors have been described. The vascular endothelial growth factor (VEGF) and its receptors are major contributors to normal mammalian vascular development. These receptors include VEGFR-1, VEGFR-2, VEGFR-3, neuropilin-1 (NRP1), and NRP2. The function of these genes have been determined to some degree in mouse gene targeting studies. These knockouts are embryonically lethal, and early death can be attributed in part to lack of normal blood and lymphatic vessel development. More recently, it has been demonstrated that zebrafish are an excellent model for studying the genes and proteins that regulate embryonic vascular development. Zebrafish have a number of advantages compared to mice, including rapid embryonic development and the ability to examine and manipulate embryos outside of the animal. In this review, we describe some of the earlier mouse VEGF/receptor functional studies and emphasize the development of the zebrafish vasculature. We describe the zebrafish vasculature, zebrafish VEGF and VEGF receptors, advantages of the zebrafish model, resources, and methods of determining growth factor and receptor function.
血管发育是如何调控的,这一问题备受关注。人们已经描述了多种血管生长因子及其受体。血管内皮生长因子(VEGF)及其受体是正常哺乳动物血管发育的主要贡献者。这些受体包括VEGFR - 1、VEGFR - 2、VEGFR - 3、神经纤毛蛋白-1(NRP1)和NRP2。在小鼠基因靶向研究中,这些基因的功能已在一定程度上得以确定。这些基因敲除会导致胚胎致死,早期死亡部分可归因于正常血管和淋巴管发育的缺失。最近,有研究表明斑马鱼是研究调控胚胎血管发育的基因和蛋白质的优秀模型。与小鼠相比,斑马鱼具有许多优势,包括胚胎发育迅速以及能够在动物体外检查和操作胚胎。在这篇综述中,我们描述了一些早期的小鼠VEGF/受体功能研究,并着重介绍斑马鱼血管系统的发育。我们描述了斑马鱼的血管系统、斑马鱼VEGF和VEGF受体、斑马鱼模型的优势、资源以及确定生长因子和受体功能的方法。