Minehata Ken-Ichi, Kawahara Atsuo, Suzuki Takeshi
Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Biochem Biophys Res Commun. 2008 Oct 3;374(4):647-52. doi: 10.1016/j.bbrc.2008.07.075. Epub 2008 Jul 24.
The differentiation of endothelial cells is tightly connected with the formation of blood vessels during vertebrate development. The signaling pathways mediated by vascular endothelial growth factor (vegf) are required for these processes. Here we show that a proto-oncogene, meis1, plays important roles in the vascular development in zebrafish. Knockdown of meis1 by anti-sense meis1 morpholino (meis1 MO) led to the impairment of intersegmental vessel (ISV) formation. In meis1 morphants, the expression of an artery marker was reduced in dorsal aorta (DA), and the expression of vein markers was expanded in DA and posterior cardinal vein (PCV), suggesting the defects on artery development. Furthermore, the expression of vegf receptor, flk1, was significantly decreased in these embryos. Interestingly, flk1 MO-injected embryos exhibited similar defects as meis1 morphants. Thus, these results implicate that meis1 is a novel regulator involved in endothelial cell development, presumably affecting the vegf signaling pathway.
在脊椎动物发育过程中，内皮细胞的分化与血管形成紧密相关。血管内皮生长因子（VEGF）介导的信号通路是这些过程所必需的。在此我们表明，原癌基因Meis1在斑马鱼血管发育中起重要作用。用反义Meis1吗啉代寡核苷酸（Meis1 MO）敲低Meis1会导致节间血管（ISV）形成受损。在Meis1 morphants中，动脉标记物在背主动脉（DA）中的表达降低，静脉标记物在DA和后主静脉（PCV）中的表达增加，提示动脉发育存在缺陷。此外，这些胚胎中VEGF受体Flk1的表达显著降低。有趣的是，注射Flk1 MO的胚胎表现出与Meis1 morphants类似的缺陷。因此，这些结果表明Meis1是参与内皮细胞发育的一种新型调节因子，可能影响VEGF信号通路。
