1. Maternal and Zygotic Sphingosine Kinase 2 Are Indispensable for Cardiac Development in Zebrafish
- Author
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Hirotaka Matsumoto, Junken Aoki, Yu Hisano, Asuka Inoue, Hirohito Kotani, Kiyohito Taimatsu, Rie Ohga, Michiyo Okudaira, and Atsuo Kawahara
- Subjects
Zygote ,Molecular Sequence Data ,Mutant ,Biochemistry ,chemistry.chemical_compound ,Pregnancy ,Animals ,Amino Acid Sequence ,Molecular Biology ,Zebrafish ,S1PR2 ,Genetics ,Sequence Homology, Amino Acid ,biology ,Sphingosine ,Sphingosine Kinase 2 ,Heart ,Cell Biology ,Lipid signaling ,biology.organism_classification ,Lipids ,Cell biology ,Isoenzymes ,Phosphotransferases (Alcohol Group Acceptor) ,SPHK2 ,chemistry ,Mutation ,Maternal to zygotic transition ,Female ,lipids (amino acids, peptides, and proteins) - Abstract
Sphingosine 1-phosphate (S1P) is synthesized from sphingosine by sphingosine kinases (SPHK1 and SPHK2) in invertebrates and vertebrates, whereas specific receptors for S1P (S1PRs) selectively appear in vertebrates, suggesting that S1P acquires novel functions in vertebrates. Because the developmental functions of SPHK1 and SPHK2 remain obscure in vertebrates, we generated sphk1 or sphk2 gene-disrupted zebrafish by introducing premature stop codons in their coding regions using transcription activator-like effector nucleases. Both zygotic sphk1 and sphk2 zebrafish mutants exhibited no obvious developmental defects and grew to adults. The maternal-zygotic sphk2 mutant (MZsphk2), but not the maternal-zygotic sphk1 mutant and maternal sphk2 mutant, had a defect in the cardiac progenitor migration and a concomitant decrease in S1P level, leading to a two-heart phenotype (cardia bifida). Cardia bifida in MZsphk2, which was rescued by injecting sphk2 mRNA, was a phenotype identical to that of zygotic mutants of the S1P transporter spns2 and S1P receptor s1pr2, indicating that the Sphk2-Spns2-S1pr2 axis regulates the cardiac progenitor migration in zebrafish. The contribution of maternally supplied lipid mediators during vertebrate organogenesis presents as a requirement for maternal-zygotic Sphk2.
- Published
- 2015
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