The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors.
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.
Kawahara
Atsuo
A
Department of Structural Analysis, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan. atsuo@ri.ncvc.go.jp
Nishi
Tsuyoshi
T
Hisano
Yu
Y
Fukui
Hajime
H
Yamaguchi
Akihito
A
Mochizuki
Naoki
N
D000818:Animals; D030801:Animals, Genetically Modified; D001757:Blastomeres / Q000378:metabolism; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D006224:Cricetinae; D003412:Cricetulus; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D047108:Embryonic Development; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000196:embryology; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016376:Oligonucleotides, Antisense; D038081:Organogenesis; D015398:Signal Transduction; D019170:Somites / Q000196:embryology / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D008246:Lysophospholipids; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D029961:Zebrafish Proteins; C534950:sphingolipid transporter 2, zebrafish; C060506:sphingosine 1-phosphate; D013110:Sphingosine