title: G protein-coupled receptors Flop1 and Flop2 inhibit Wnt/β-catenin signaling and are essential for head formation in Xenopus.
abstract: Patterning of the vertebrate anterior-posterior axis is regulated by the coordinated action of growth factors whose effects can be further modulated by upstream and downstream mediators and the cross-talk of different intracellular pathways. In particular, the inhibition of the Wnt/β-catenin signaling pathway by various factors is critically required for anterior specification. Here, we report that Flop1 and Flop2 (Flop1/2), G protein-coupled receptors related to Gpr4, contribute to the regulation of head formation by inhibiting Wnt/β-catenin signaling in Xenopus embryos. Using whole-mount in situ hybridization, we showed that flop1 and flop2 mRNAs were expressed in the neural ectoderm during early gastrulation. Both the overexpression and knockdown of Flop1/2 resulted in altered embryonic head phenotypes, while the overexpression of either Flop1/2 or the small GTPase RhoA in the absence of bone morphogenetic protein (BMP) signaling resulted in ectopic head induction. Examination of the Flops' function in Xenopus embryo animal cap cells showed that they inhibited Wnt/β-catenin signaling by promoting β-catenin degradation through both RhoA-dependent and -independent pathways in a cell-autonomous manner. These results suggest that Flop1 and Flop2 are essential regulators of Xenopus head formation that act as novel inhibitory components of the Wnt/β-catenin signaling pathway.
authors.affiliation: Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Department of Basic Biology, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Miyagi
authors.affiliation: Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Negishi
authors.affiliation: Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan.
authors.forename: Takamasa S
authors.initials: TS
authors.lastname: Yamamoto
authors.affiliation: Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan; Department of Basic Biology, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan. Electronic address: nueno@nibb.ac.jp.
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D047108:Embryonic Development; D006257:Head / Q000196:embryology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D019485:Bone Morphogenetic Proteins; C502565:Flop protein, Xenopus; D043562:Receptors, G-Protein-Coupled; D029867:Xenopus Proteins; D020742:rhoA GTP-Binding Protein
keywords: Flop; G protein-coupled receptor (GPCR); Head formation; RhoA; Wnt/β-catenin signaling; Xenopus laevis