Moser Martin, Yu Qingming, Bode Christoph, Xiong Jing-Wei, Patterson Cam
University of Freiburg, Internal Medicine III, Hugstetter Strasse 55, 79106 Freiburg, Germany.
J Mol Cell Cardiol. 2007 Sep;43(3):243-53. doi: 10.1016/j.yjmcc.2007.05.008. Epub 2007 May 18.
For the proper development of vertebrate embryos as well as for survival of the adult organism, it is essential to form a functional vascular system. Molecules involved in this process are members of highly conserved families of proteins that exert conserved functions across species. Bone morphogenetic proteins (BMP) are extracellular factors that are regulated by extracellular modulators and bind to BMP receptors, which in turn activate intracellular signaling cascades. BMPs are necessary not only for induction of endothelial and hematopoietic lineages but also for further endothelial and hematopoietic cell differentiation. Previously, we identified BMPER (BMP endothelial cell precursor derived regulator) and demonstrated its spatiotemporal expression at sites of vasculogenesis and direct modulation of BMP activity. To directly investigate the role of BMPER in vascular development, we cloned the BMPER ortholog in zebrafish (zbmper). It is expressed at sites of high BMP activity, including vascular precursor cells located in the aortic arches and the intermediate cell mass during zebrafish embryonic development. Knockdown of zbmper results in a dorsalized phenotype, a reduced number of gata1 expressing hematopoietic precursor cells and of circulating blood cells as well as in a vascular phenotype. The generation of the caudal vein is compromised and the pattern guiding of the intersomitic vessels is disturbed, indicating that zbmper is required for early steps in vascular pattern formation and hematopoiesis in zebrafish.
对于脊椎动物胚胎的正常发育以及成体生物的存活而言,形成一个功能正常的血管系统至关重要。参与这一过程的分子是高度保守的蛋白质家族成员,它们在物种间发挥着保守的功能。骨形态发生蛋白(BMP)是细胞外因子,受细胞外调节剂调控,并与BMP受体结合,进而激活细胞内信号级联反应。BMP不仅对于内皮细胞和造血谱系的诱导是必需的,而且对于内皮细胞和造血细胞的进一步分化也是必需的。此前,我们鉴定出了BMPER(BMP内皮细胞前体衍生调节剂),并证明了它在血管生成部位的时空表达以及对BMP活性的直接调节作用。为了直接研究BMPER在血管发育中的作用,我们克隆了斑马鱼中的BMPER直系同源基因(zbmper)。它在高BMP活性部位表达,包括斑马鱼胚胎发育过程中位于主动脉弓和中间细胞团的血管前体细胞。敲低zbmper会导致背化表型、表达gata1的造血前体细胞和循环血细胞数量减少以及血管表型。尾静脉的生成受损,体节间血管的模式引导受到干扰,这表明zbmper是斑马鱼血管模式形成和造血早期步骤所必需的。