The Rac1 Regulator ELMO1 Controls Vascular Morphogenesis in Zebrafish
The Rac1 Regulator ELMO1 Controls Vascular Morphogenesis in Zebrafish
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DOI：
10.1161/circresaha.109.213983
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发表时间：
2010-07-09
影响因子：
20.1
通讯作者：
Kroll, Jens
中科院分区：
文献类型：
--
作者：
Epting, Daniel;Wendik, Bjoern;Kroll, Jens
基本原理：血管生成受小GT3 Rac 1调节。ELMO 1/DOCK 180复合物形成Rac 1的鸟嘌呤核苷酸交换因子，调节其在不同生物系统中的细胞迁移过程中的活化。目的：研究ELMO 1/DOCK 180在血管发育中的功能。方法和结果：原位杂交研究证实elmo 1在斑马鱼血管和神经元中表达。基于morpholino的表达沉默elmo 1严重损害了血管系统的形成，包括体间血管，背纵吻合血管，脊索旁血管，和tg（fli 1：EGFP）胚胎中胸导管的发育。从机制上讲，我们确定Netrin-1及其受体Unc 5 B作为ELMO 1/DOCK 180复合物的上游激活剂，调节其功能相互作用，并导致Rac 1激活内皮细胞和血管形成在zebrafish.Conclusions：我们的数据已经确定了一种新的信号级联调节血管形成在斑马鱼。(Circ Res. 2010; 107：45-55）。
Rationale: Angiogenesis is regulated by the small GTPase Rac1. The ELMO1/DOCK180 complex forms a guanine nucleotide exchange factor for Rac1, regulating its activation during cell migration in different biological systems.Objective: To investigate the function of ELMO1/DOCK180 in vascular development.Methods and Results: In situ hybridization studies for elmo1 identified a vascular and neuronal expression in zebrafish. Morpholino-based expression silencing of elmo1 severely impaired the formation of the vasculature, including intersomitic vessels, the dorsal longitudinal anastomotic vessel, the parachordal vessel, and the development of the thoracic duct in tg(fli1:EGFP) embryos. Mechanistically, we identified Netrin-1 and its receptor Unc5B as upstream activators of the ELMO1/DOCK180 complex, regulating its functional interaction and leading to Rac1 activation in endothelial cells and vessel formation in zebrafish.Conclusions: Our data have identified a novel signaling cascade regulating vasculature formation in zebrafish. (Circ Res. 2010; 107: 45-55.)