title: Zebrafish heart development is regulated via glutaredoxin 2 dependent migration and survival of neural crest cells.
abstract: Glutaredoxin 2 is a vertebrate specific oxidoreductase of the thioredoxin family of proteins modulating the intracellular thiol pool. Thereby, glutaredoxin 2 is important for specific redox signaling and regulates embryonic development of brain and vasculature via reversible oxidative posttranslational thiol modifications. Here, we describe that glutaredoxin 2 is also required for successful heart formation. Knock-down of glutaredoxin 2 in zebrafish embryos inhibits the invasion of cardiac neural crest cells into the primary heart field. This leads to impaired heart looping and subsequent obstructed blood flow. Glutaredoxin 2 specificity of the observed phenotype was confirmed by rescue experiments. Active site variants of glutaredoxin 2 revealed that the (de)-glutathionylation activity is required for proper heart formation. Our data suggest that actin might be one target during glutaredoxin 2 regulated cardiac neural crest cell migration and embryonic heart development. In summary, this work represents further evidence for the general importance of redox signaling in embryonic development and highlights additionally the importance of glutaredoxin 2 during embryogenesis.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden ; Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Life Science Center, Merowinger Platz 1, Düsseldorf, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Berndt
authors.affiliation: Molecular Proteomics Laboratory, Heinrich-Heine-University, BMFZ, Düsseldorf, Germany.
authors.forename: Gereon
authors.initials: G
authors.lastname: Poschmann
authors.affiliation: Molecular Proteomics Laboratory, Heinrich-Heine-University, BMFZ, Düsseldorf, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Stühler
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Holmgren
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden ; Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Bräutigam
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D054477:Glutaredoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000254:growth & development*; D009206:Myocardium / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015027:Zebrafish / Q000254:growth & development*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D054477:Glutaredoxins; D034741:RNA, Small Interfering; D029961:Zebrafish Proteins
keywords: A, atrium; CCV, common cardinal vein; CNC, cardiac neural crest; Cardiac development; GSH, glutathione; Glutaredoxin; Grx, glutaredoxin; Migration; NC, neural crest; S-glutathionylation; V, ventricle; Zebrafish; zf, zebrafish