title: Glycogen synthase kinase 3 beta in somites plays a role during the angiogenesis of zebrafish embryos.
abstract: Glycogen synthase kinase 3 beta (Gsk3b) acts as a negative modulator in endothelial cells through the Wnt/β-catenin/PI3K/AKT/Gsk3b axis in cancer-induced angiogenesis. However, the function of Gsk3b during embryonic angiogenesis remains unclear. Here, either gsk3b knockdown by morpholino or Gsk3b loss of activity by LiCl treatment had serious phenotypic consequences, such as defects in the positioning and patterning of intersegmental blood vessels and reduction of vegfaa121 and vegfaa165 transcripts. In embryos treated with the phosphatidylinositol 3-kinase inhibitor, angiogenesis was severely inhibited, along with reduced Wnt, phosphorylated AKT and phosphorylated Gsk3b, suggesting that the remaining Gsk3b in somites could still degrade β-catenin, resulting in decreased vascular endothelial growth factor Aa(VegfAa) expression. However, in gsk3b-mRNA-overexpressed embryos, intersegmental vessels ectopically sprouted by the increase in phosphorylated-Gsk3b which prevented the degradation of β-catenin and promoted the increase in phosphorylated AKT activity, thus increasing VegfAa expression in somites. Interestingly, the Gsk3b-dependent cross-talk between PI3K/AKT and Wnt/β-catenin suggests that Wnt/β-catenin and PI3K/AKT interaction controls embryonic angiogenesis by a positive feedback loop rather than a hierarchical framework such as that found in cancer-induced angiogenesis. Thus, both active and inactive forms of Gsk3b mediate the cooperative signaling between Wnt/β-catenin and PI3K/AKT to control VegfAa expression in somites during angiogenesis in zebrafish embryos.
authors: Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan.
authors: Hung-Chieh
authors: HC
authors: Lee
authors: Yi-Zhen
authors: YZ
authors: Lin
authors: Yen-Ting
authors: YT
authors: Lai
authors: Wei-Jhen
authors: WJ
authors: Huang
authors: Jia-Rung
authors: JR
authors: Hu
authors: Jen-Ning
authors: JN
authors: Tsai
authors: Huai-Jen
authors: HJ
authors: Tsai
mesh_terms: D000818:Animals; D002970:Cleavage Stage, Ovum / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000201:enzymology; D004730:Endothelium, Vascular / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D018919:Neovascularization, Physiologic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000201:enzymology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: Gsk3b; angiogenesis; somite; vascular endothelial growth factor; zebrafish