Mutation in utp15 disrupts vascular patterning in a p53-dependent manner in zebrafish embryos.
Mutation in utp15 disrupts vascular patterning in a p53-dependent manner in zebrafish embryos.
复制标题
DOI：
10.1371/journal.pone.0025013
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Chen JN
中科院分区：
文献类型：
--
作者：
Mouillesseaux K;Chen JN
血管生成是一个过程，通过这个过程，高度分支和功能性的脉管系统从主要血管中产生，为发育中的组织提供营养物质，氧气，并清除代谢废物。在胚胎发生期间，血管形成依赖于促血管生成信号和抗血管生成信号之间的严格调节的平衡，并且血管生成的失败导致胚胎死亡。以斑马鱼为模式生物，我们试图鉴定影响正常血管模式的基因。在正向遗传筛选中，我们鉴定了突变体LA 1908，其在早期胚胎发生期间表现出大量凋亡，动脉-静脉特异性的几个标志物的异常表达，节间血管（ISV）的延迟血管生成萌芽，以及尾静脉丛（CVP）的畸形，表明LA 1908在细胞存活和血管生成中的关键作用。遗传作图和测序鉴定了LA 1908突变胚胎中utp 15外显子11前的剪接位点中的G到A转变。野生型utp 15 mRNA的过表达抑制所有观察到的突变体表型，表明utp 15和LA 1908之间的因果关系。此外，我们发现，注射吗啉代寡核苷酸抑制p53翻译防止细胞死亡和挽救血管异常，表明p53是下游的Utp 15缺陷介导的LA 1908表型。总之，我们的数据表明，Utp 15缺陷对细胞存活和血管系统的正常模式的早期胚胎的影响，并强调了p53在发育中的胚胎中的抗血管生成作用。
Angiogenesis is the process by which the highly branched and functional vasculature arises from the major vessels, providing developing tissues with nutrients, oxygen, and removing metabolic waste. During embryogenesis, vascular patterning is dependent on a tightly regulated balance between pro- and anti-angiogenic signals, and failure of angiogenesis leads to embryonic lethality. Using the zebrafish as a model organism, we sought to identify genes that influence normal vascular patterning. In a forward genetic screen, we identified mutant LA1908, which manifests massive apoptosis during early embryogenesis, abnormal expression of several markers of arterial-venous specification, delayed angiogenic sprouting of the intersegmental vessels (ISV), and malformation of the caudal vein plexus (CVP), indicating a critical role for LA1908 in cell survival and angiogenesis. Genetic mapping and sequencing identified a G to A transition in the splice site preceding exon 11 of utp15 in LA1908 mutant embryos. Overexpression of wild type utp15 mRNA suppresses all observed mutant phenotypes, demonstrating a causative relationship between utp15 and LA1908. Furthermore, we found that injecting morpholino oligonucleotides inhibiting p53 translation prevents cell death and rescues the vascular abnormalities, indicating that p53 is downstream of Utp15 deficiency in mediating the LA1908 phenotypes. Taken together, our data demonstrate an early embryonic effect of Utp15 deficiency on cell survival and the normal patterning of the vasculature and highlight an anti-angiogenic role of p53 in developing embryos.
登录
查看更多内容
影响因子：
3.7
作者：
Danilova N;Kumagai A;Lin J
通讯作者：
Lin J
DOI：
10.1073/pnas.0506886103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Covassin, LD;Villefranc, JA;Lawson, ND
通讯作者：
Lawson, ND
影响因子：
64.8
作者：
Dragon, F;Gallagher, JEG;Baserga, SJ
通讯作者：
Baserga, SJ
影响因子：
64.5
作者：
RASTINEJAD, F;POLVERINI, PJ;BOUCK, NP
通讯作者：
BOUCK, NP
影响因子：
56.9
作者：
DAMERON, KM;VOLPERT, OV;BOUCK, N
通讯作者：
BOUCK, N