RRC ID 4102
Author Kawahara A, Nishi T, Hisano Y, Fukui H, Yamaguchi A, Mochizuki N.
Title The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors.
Journal Science
Abstract Sphingosine-1-phosphate (S1P) is a secreted lipid mediator that functions in vascular development; however, it remains unclear how S1P secretion is regulated during embryogenesis. We identified a zebrafish mutant, ko157, that displays cardia bifida (two hearts) resembling that in the S1P receptor-2 mutant. A migration defect of myocardial precursors in the ko157 mutant is due to a mutation in a multipass transmembrane protein, Spns2, and can be rescued by S1P injection. We show that the export of S1P from cells requires Spns2. spns2 is expressed in the extraembryonic tissue yolk syncytial layer (YSL), and the introduction of spns2 mRNA in the YSL restored the cardiac defect in the ko157 mutant. Thus, Spns2 in the YSL functions as a S1P transporter in S1P secretion, thereby regulating myocardial precursor migration.
Volume 323(5913)
Pages 524-7
Published 2009-1-23
DOI 10.1126/science.1167449
PII 1167449
PMID 19074308
MeSH Animals Animals, Genetically Modified Blastomeres / metabolism CHO Cells Carrier Proteins / chemistry Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Movement Cricetinae Cricetulus Embryo, Nonmammalian / cytology Embryo, Nonmammalian / metabolism* Embryonic Development Heart / embryology* Heart Defects, Congenital / embryology Humans Lysophospholipids / metabolism* Membrane Proteins / chemistry Membrane Proteins / genetics Membrane Proteins / metabolism* Mesoderm / metabolism Mice Molecular Sequence Data Mutation Oligonucleotides, Antisense Organogenesis Signal Transduction Somites / embryology Somites / metabolism Sphingosine / analogs & derivatives* Sphingosine / metabolism Zebrafish / embryology* Zebrafish / genetics Zebrafish Proteins / chemistry Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 41.063
Times Cited 168
Zebrafish ko157 ko157/cmlc2:mRFP