Molecular mechanism of hematopoietic and cardiovascular development in zebrafish

我的目的是揭示新的关键分子在血管和心脏的发展，通过表征新的心血管斑马鱼突变体。在ko 095突变体中，除了神经管外，还观察到节间血管的异常分支。此外，VEGF（血管内皮生长因子）的表达增加，其是血管生成的关键因子，导致ko 095突变体中过度的血管重塑。我发现ko 095的基因是Sars（Seryl-tRNA合成酶），它是蛋白质合成所必需的酶：Sars具有参与血管生成的新功能。另一方面，ko 157突变体表现出心脏祖细胞迁移的障碍，导致称为心裂的两个心脏。我发现，负责ko 157的基因是一种十二通道跨膜结构域蛋白Spns 2（Spnster样2）。Spns 2的生化分析表明，Spns 2作为鞘脂介质，鞘氨醇-1-磷酸（S1 P）的转运蛋白。因此，我发现Sars和Spns 2分别在斑马鱼的血管和心脏发育中发挥重要作用。

I aimed to reveal novel key molecules in vascular and cardiac development by the characterization of novel cardiovascular zebrafish mutants. In the ko095 mutants, aberrant branching of intersegmental vessels besides of the neural tube was observed. Further, the increased expression of VEGF (vascular endothelial growth factor), which is a key factor in angiogenesis, caused the excessive vascular remodeling in the ko095 mutant. I found that the gene responsible for the ko095 is Sars (Seryl-tRNA synthetase) that is known as an enzyme essential for protein synthesis: Sars possesses a novel function involved in angiogenesis. On the other hand, the ko157 mutant exhibited the impairment of cardiac progenitor migration, resulting in two hearts known as cardia bifida. I found that the gene responsible for the ko157 is a twelve-pass transmembrane-domain protein Spns2 (Spnster-like 2). Biochemical analysis of Spns2 presented that Spns2 functions as a transporter of a sphingolipid mediator, sphingosine-1-phosphate (S1P). Thus, I found that Sars and Spns2 play important roles in vascular and cardiac development in zebrafish, respectively.