Center for Biomedicine and Medical Technology Mannheim, Research Division Vascular Biology of the Medical Faculty Mannheim, Heidelberg University and the German Cancer Research Center (DKFZ-ZMBH Alliance) Heidelberg, Mannheim, Germany.
Circ Res. 2010 Jul 9;107(1):45-55. doi: 10.1161/CIRCRESAHA.109.213983. Epub 2010 May 13.
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.
To investigate the function of ELMO1/DOCK180 in vascular development.
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.
Our data have identified a novel signaling cascade regulating vasculature formation in zebrafish.
血管生成受小 GTPase Rac1 的调节。ELMO1/DOCK180 复合物作为 Rac1 的鸟嘌呤核苷酸交换因子，在不同的生物系统中调节其在细胞迁移过程中的激活。
研究 ELMO1/DOCK180 在血管发育中的作用。
原位杂交研究表明 zebrafish 中存在血管和神经元表达 elmo1。elmo1 的基于 morpholino 的表达沉默严重损害了血管的形成，包括体节间血管、背侧纵向吻合血管、副脊索血管和 tg(fli1:EGFP)胚胎中的胸导管发育。从机制上讲，我们鉴定出 Netrin-1 和其受体 Unc5B 作为 ELMO1/DOCK180 复合物的上游激活物，调节其功能相互作用，并导致内皮细胞中 Rac1 的激活和 zebrafish 中血管的形成。
我们的数据确定了一个新的信号级联反应，调节 zebrafish 中的血管形成。
