Molecular mechanism of hematopoietic and cardiovascular development in zebrafish

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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.