title: Comprehensive analysis of sphingosine-1-phosphate receptor mutants during zebrafish embryogenesis.
abstract: The lipid mediator sphingosine-1-phosphate (S1P) regulates various physiological and pathological phenomena such as angiogenesis and oncogenesis. Secreted S1P associates with the G-protein-coupled S1P receptors (S1PRs), leading to the activation of downstream signaling molecules. In mammals, five S1prs have been identified and the genetic disruption of a single S1pr1 gene causes vascular defects. In zebrafish, seven s1prs have been isolated. We found that individual s1prs showed unique expression patterns with some overlapping expression domains during early embryogenesis. We generated all s1pr single-mutant zebrafish by introducing premature stop codons in their coding regions using transcription activator-like effector nucleases and analyzed their phenotypes during early embryogenesis. Zygotic s1pr1, s1pr3a, s1pr3b, s1pr4, s1pr5a and s1pr5b mutants showed no developmental defects and grew into adults, whereas zygotic s1pr2 mutant showed embryonic lethality with a cardiac defect, showing quite distinct embryonic phenotypes for individual S1pr mutants between zebrafish and mouse. We further generated maternal-zygotic s1pr1, s1pr3a, s1pr3b, s1pr4, s1pr5a and s1pr5b mutants and found that these maternal-zygotic mutants also showed no obvious developmental defects, presumably suggesting the redundant functions of the S1P receptor-mediated signaling in zebrafish.
authors.affiliation: Laboratory for Developmental Gene Regulation, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.|Laboratory for Cardiovascular Molecular Dynamics, Quantitative Biology Center, RIKEN, 6-2-3 Furuedai, Suita, Osaka, 565-0074, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hisano
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.|PRESTO, Japan Science and Technology Agency, Kawaguchi, 332-8613, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Inoue
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: Laboratory for Cardiovascular Molecular Dynamics, Quantitative Biology Center, RIKEN, 6-2-3 Furuedai, Suita, Osaka, 565-0074, Japan.|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: Satoshi
authors.initials: S
authors.lastname: Ota
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: 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 Cardiovascular Molecular Dynamics, Quantitative Biology Center, RIKEN, 6-2-3 Furuedai, Suita, Osaka, 565-0074, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Muraki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, 332-8613, Japan.
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.affiliation: Laboratory for Cardiovascular Molecular Dynamics, Quantitative Biology Center, RIKEN, 6-2-3 Furuedai, Suita, Osaka, 565-0074, Japan.|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: Atsuo
authors.initials: A
authors.lastname: Kawahara
mesh_terms: D058500:Animal Fins / Q000502:physiology; D000818:Animals; D047108:Embryonic Development; D051379:Mice; D009154:Mutation; D049349:Receptors, Lysosphingolipid / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology
chemical_list: D049349:Receptors, Lysosphingolipid