title: Activation and roles of ALK4/ALK7-mediated maternal TGFbeta signals in zebrafish embryo.
abstract: Activin, Nodal, and Vg1, members of the transforming growth factor beta (TGFbeta) superfamily, transduce signal through type I receptors ALK4 or ALK7 and play important roles in mesoderm induction and patterning during vertebrate embryogenesis. However, the timing and magnitude of the ALK4/ALK7-mediated maternal TGFbeta signals are not clear. SB-431542 is identified as an inhibitor of the ALK4/ALK5/ALK7-mediated TGFbeta signals and its specificity in vertebrate embryos has not been reported. We demonstrate that SB-431542 is able to specifically and reproducibly block the Smad2/3-mediated TGFbeta signals in zebrafish embryo. Embryos exposed to SB-431542 exhibit various defects phenocopying Nodal-deficient mutants. SB-431542 treatments starting at different cell cycles before the midblastula transition lead to different degrees of developmental defects in mesoderm induction and patterning, suggesting that maternal TGFbeta signals are activated right after fertilization and required for mesoderm formation and patterning.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Sun
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.forename: Yi
authors.initials: Y
authors.lastname: Gu
authors.forename: Ye-Guang
authors.initials: YG
authors.lastname: Chen
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
mesh_terms: D029404:Activin Receptors / Q000378:metabolism*; D030201:Activin Receptors, Type I; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D036703:Blastula / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D004149:Dioxoles / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014714:Vertebrates / Q000196:embryology / Q000235:genetics; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D029404:Activin Receptors; D030201:Activin Receptors, Type I; C512426:acvr1ba protein, zebrafish