Vascular endothelial growth factor signaling regulates the segregation of artery and vein via ERK activity during vascular development.
Vascular endothelial growth factor signaling regulates the segregation of artery and vein via ERK activity during vascular development.
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DOI：
10.1016/j.bbrc.2012.12.076
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发表时间：
2013-01-25
影响因子：
3.1
通讯作者：
Jin, Suk-Won
中科院分区：
文献类型：
--
作者：
Kim, Se-Hee;Schmitt, Christopher E.;Woolls, Melissa J.;Holland, Melinda B.;Kim, Jun-Dae;Jin, Suk-Won
背主动脉和尾静脉这两条轴向血管的分离是血管系统发育过程中最早发生的模式化事件之一。尽管这一过程的重要性和最近的进展，我们在发展过程中的血管图案的理解，协调分离的轴向血管的分子机制仍然在很大程度上难以捉摸。在这份报告中，我们发现血管内皮生长因子-A（Vegf-A）信号调节背主动脉和轴静脉的分离在发育过程中。抑制Vegf-A途径组分，包括配体Vegf-A及其同源受体Kdrl，导致斑马鱼胚胎中轴血管分离失败。同样，化学抑制促分裂原活化蛋白激酶激酶（Map 2k 1）/细胞外信号调节激酶（Erk）和磷脂酰肌醇3-激酶（PI 3 K），它们是Vegf-A信号通路的下游效应子，导致两个轴向血管融合。此外，我们发现，通过在具有降低水平的Vegf-A信号传导的胚胎中过表达组成型活性MEK来恢复Erk活性可以挽救轴向血管分离中的缺陷。综上所述，我们的数据表明，轴向血管的分离需要Vegf-A信号传导的功能，Erk可能在这个过程中作为主要的下游效应子发挥作用。
Segregation of two axial vessels, the dorsal aorta and caudal vein, is one of the earliest patterning events occur during development of vasculature. Despite the importance of this process and recent advances in our understanding on vascular patterning during development, molecular mechanisms that coordinate the segregation of axial vessels remain largely elusive. In this report, we find that Vascular Endothelial Growth Factor-A (Vegf-A) signaling regulates the segregation of dorsal aorta and axial vein during development. Inhibition of Vegf-A pathway components including ligand Vegf-A and its cognate receptor Kdrl, caused failure in segregation of axial vessels in zebrafish embryos. Similarly, chemical inhibition of Mitogen-activated protein kinase kinase (Map2k1)/Extracellular-signal-regulated kinases (Erk) and Phosphatidylinositol 3-kinases (PI3K), which are downstream effectors of Vegf-A signaling pathway, led to the fusion of two axial vessels. Moreover, we find that restoring Erk activity by over-expression of constitutively active MEK in embryos with a reduced level of Vegf-A signaling can rescue the defects in axial vessel segregation. Taken together, our data show that segregation of axial vessels requires the function of Vegf-A signaling, and Erk may function as the major downstream effector in this process.
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大脑血管畸形的生物学。
影响因子：
8.3
作者：
Leblanc GG;Golanov E;Awad IA;Young WL;Biology of Vascular Malformations of the Brain NINDS Workshop Collaborators
通讯作者：
Biology of Vascular Malformations of the Brain NINDS Workshop Collaborators
影响因子：
10.5
作者：
Lawson, ND;Mugford, JW;Weinstein, BM
通讯作者：
Weinstein, BM
影响因子：
4.8
作者：
Favata, MF;Horiuchi, KY;Trzaskos, JM
通讯作者：
Trzaskos, JM
影响因子：
2.7
作者：
Pendeville, Helene;Winandy, Marie;Voz, Marianne L.
通讯作者：
Voz, Marianne L.
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