BACKGROUND C-lectin family 14 Member A (Clec14a) is a transmembrane protein specifically expressed in vascular endothelial cells during embryogenesis. Previous in vitro and in vivo studies have provided conflicting data regarding Clec14a role in promoting or inhibiting angiogenesis, therefore its functional role in vascular development remains poorly understood. RESULTS Here we have generated a novel clec14a mutant allele in zebrafish embryos using TALEN genome editing. clec14a mutant embryos exhibit partial defects and delay in the sprouting of intersegmental vessels. These defects in angiogenesis are greatly increased upon the knockdown of a structurally related C1qr protein. Furthermore, a partial knockdown of an ETS transcription factor Etv2 results in a synergistic effect with the clec14a mutation and inhibits expression of early vascular markers in endothelial progenitor cells, arguing that clec14a is involved in promoting vasculogenesis. In addition, Clec14a genetically interacts with Vegfa signaling. A partial knockdown of Vegfaa function in the clec14a mutant background resulted in a synergistic inhibition of intersegmental vessel sprouting. CONCLUSIONS These results argue that clec14a is involved in both vasculogenesis and angiogenesis, and suggest that Clec14a genetically interacts with Etv2 and Vegf signaling during vascular development in zebrafish embryos.

中文翻译：

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Clec14a在斑马鱼的血管生成和血管生成过程中与Etv2和Vegf信号转导基因相互作用。

背景技术C-凝集素家族14成员A（Clec14a）是在胚胎发生过程中在血管内皮细胞中特异性表达的跨膜蛋白。先前的体外和体内研究提供了有关Clec14a在促进或抑制血管生成中作用的相互矛盾的数据，因此，其在血管发育中的功能作用仍然知之甚少。结果在这里，我们使用TALEN基因组编辑在斑马鱼胚胎中产生了一个新的clec14a突变等位基因。clec14a突变体胚胎在节间血管的发芽中表现出部分缺陷和延迟。敲除结构相关的C1qr蛋白后，血管生成中的这些缺陷会大大增加。此外，ETS转录因子Etv2的部分敲低与clec14a突变产生协同效应，并抑制内皮祖细胞中早期血管标志物的表达，认为clec14a参与促进血管生成。另外，Clec14a与Vegfa信号转导具有基因相互作用。在clec14a突变体背景中，部分Vegfaa功能被抑制导致了节间血管发芽的协同抑制。结论这些结果表明，clec14a参与了血管生成和血管生成，并表明Clec14a在斑马鱼胚胎的血管发育过程中与Etv2和Vegf信号转导发生了遗传相互作用。在clec14a突变体背景中，部分Vegfaa功能被抑制导致了节间血管发芽的协同抑制。结论这些结果表明，clec14a参与了血管生成和血管生成，并表明Clec14a在斑马鱼胚胎的血管发育过程中与Etv2和Vegf信号转导发生了遗传相互作用。在clec14a突变体背景中，部分Vegfaa功能被抑制导致了节间血管发芽的协同抑制。结论这些结果表明，clec14a参与了血管生成和血管生成，并表明Clec14a在斑马鱼胚胎的血管发育过程中与Etv2和Vegf信号转导发生了遗传相互作用。