PDF(Pubmed)
Abstract：
BACKGROUND: Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in the zebrafish.
RESULTS: We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of the trunk lymphatic vessel network. Interestingly, we show that Sorbs1 interacts with the BMP pathway and could function outside of Vegfc signaling. Mechanistically, Sorbs1 controls FAK/Src signaling and subsequently impacts on the cytoskeleton processes regulated by Rac1 and RhoA GTPases. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contacts rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties.
CONCLUSIONS: Overall, using in vitro and in vivo assays, we identify Sorbs1 as an important regulator of venous and lymphatic angiogenesis independently of the Vegfc signaling axis. These results provide a better understanding of the complexity found within context-specific vascular and lymphatic development.
RESULTS: We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of the trunk lymphatic vessel network. Interestingly, we show that Sorbs1 interacts with the BMP pathway and could function outside of Vegfc signaling. Mechanistically, Sorbs1 controls FAK/Src signaling and subsequently impacts on the cytoskeleton processes regulated by Rac1 and RhoA GTPases. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contacts rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties.
CONCLUSIONS: Overall, using in vitro and in vivo assays, we identify Sorbs1 as an important regulator of venous and lymphatic angiogenesis independently of the Vegfc signaling axis. These results provide a better understanding of the complexity found within context-specific vascular and lymphatic development.
摘要：
背景：淋巴管生成，淋巴管的形成，与静脉血管的发育密切相关，在细胞和分子水平。这里,我们确定了Sorbs1的新作用，Sorbs1是SoHo家族细胞骨架衔接蛋白的创始成员，斑马鱼的血管和淋巴发育。
结果：我们表明，Sorbs1是继发性发芽和特异性衍生自轴向静脉的几种血管结构的出现所必需的。最值得注意的是,前体伞状淋巴结构的形成在sorbs1突变胚胎中受到影响，严重影响躯干淋巴管网络的建立。有趣的是,我们表明Sorbs1与BMP通路相互作用，并且可以在Vegfc信号传导之外发挥作用。机械上,Sorbs1控制FAK/Src信号传导，并随后影响由Rac1和RhoAGTP酶调节的细胞骨架过程。Sorbs1失活改变的细胞-细胞外基质（ECM）接触重排和细胞骨架动力学，导致内皮细胞迁移和粘附特性的特定缺陷。
结论：总体而言，使用体外和体内试验，我们确定Sorbs1是静脉和淋巴管血管生成的重要调节因子,与Vegfc信号轴无关.这些结果提供了对背景特异性血管和淋巴发育中发现的复杂性的更好理解。
结果：我们表明，Sorbs1是继发性发芽和特异性衍生自轴向静脉的几种血管结构的出现所必需的。最值得注意的是,前体伞状淋巴结构的形成在sorbs1突变胚胎中受到影响，严重影响躯干淋巴管网络的建立。有趣的是,我们表明Sorbs1与BMP通路相互作用，并且可以在Vegfc信号传导之外发挥作用。机械上,Sorbs1控制FAK/Src信号传导，并随后影响由Rac1和RhoAGTP酶调节的细胞骨架过程。Sorbs1失活改变的细胞-细胞外基质（ECM）接触重排和细胞骨架动力学，导致内皮细胞迁移和粘附特性的特定缺陷。
结论：总体而言，使用体外和体内试验，我们确定Sorbs1是静脉和淋巴管血管生成的重要调节因子,与Vegfc信号轴无关.这些结果提供了对背景特异性血管和淋巴发育中发现的复杂性的更好理解。
