title: Maternal and Zygotic Sphingosine Kinase 2 Are Indispensable for Cardiac Development in Zebrafish.
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.
authors.affiliation: From the Laboratory for Developmental Gene Regulation, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, y.hisano@riken.jp.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hisano
authors.affiliation: the Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, PRESTO and.
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
authors.affiliation: the Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Okudaira
authors.affiliation: Laboratory for Developmental Biology, Center for Medical Education and Sciences, Graduate School of Medical Science, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Taimatsu
authors.affiliation: the Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Laboratory for Developmental Biology, Center for Medical Education and Sciences, Graduate School of Medical Science, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kotani
authors.affiliation: Laboratory for Developmental Biology, Center for Medical Education and Sciences, Graduate School of Medical Science, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Ohga
authors.affiliation: the Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, CREST, Japan Science and Technology Agency and.
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.affiliation: Laboratory for Developmental Biology, Center for Medical Education and Sciences, Graduate School of Medical Science, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan akawahara@yamanashi.ac.jp.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kawahara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D006321:Heart / Q000196:embryology*; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish; D015053:Zygote / Q000201:enzymology*; D000099157:Sphingosine Kinase
chemical_list: D007527:Isoenzymes; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase
keywords: cell migration; heart development; lipid chromatography-tandem mass spectrometry (LC-MS/MS); lipid mediator signaling; lipid metabolism; lipid signaling; lipid synthesis; lipid transport; sphingolipid; sphingosine 1-phosphate (S1P); transcription activator-like effector nuclease (TALEN); zebrafish