title: Calcineurin inhibitors block dorsal-side signaling that affect late-stage development of the heart, kidney, liver, gut and somitic tissue during Xenopus embryogenesis.
abstract: Calcineurin, a calcium/calmodulin-dependent serine/threonine protein phosphatase, is a key constituent of signaling pathways involved in antigen-dependent T-cell activation and development of the mammalian heart. In addition, calcineurin constitutes a part of the Wnt/calcium-signaling pathway that regulates early stages of dorsoventral axis formation in Xenopus embryos. Although some of the Wnt family members are involved in organ formation at relatively late stages of Xenopus development, the involvement of calcineurin in the development of those organs remains unclear. In the present study, we demonstrate that calcineurin inhibitors (cyclosporine A, FK506, and FK520), but not non-calcineurin inhibitors (rapamycin and GPI1046) that bind the same intracellular receptor as that for FK506, induce edema and gut coiling disruption and exhibit teratogenesis in the kidney, heart, gut, liver, and somitic tissue during Xenopus development. The same effects were observed by injecting the calcineurin inhibitors into the dorsal side, but not ventral side, of blastomeres at the 4-cell stage, although the inhibitors did not affect dorsoventral axis formation. These results suggest that calcineurin is involved in dorsal-side signaling that leads to the formation of the heart, kidney, liver, gut and somitic tissue during Xenopus embryogenesis.
authors.affiliation: Department of Bioengineering, United Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Shokaku
authors.initials: S
authors.lastname: Kim
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Shinya
authors.initials: S
authors.lastname: Kawai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tachikawa
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000196:embryology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007422:Intestines / Q000196:embryology*; D007668:Kidney / Q000196:embryology*; D008099:Liver / Q000196:embryology*; D009024:Morphogenesis / Q000187:drug effects; D019170:Somites / Q000378:metabolism*; D051153:Wnt Proteins; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D019703:Calcineurin; D002118:Calcium