title: Noggin4 is a long-range inhibitor of Wnt8 signalling that regulates head development in Xenopus laevis.
abstract: Noggin4 is a Noggin family secreted protein whose molecular and physiological functions remain unknown. In this study, we demonstrate that in contrast to other Noggins, Xenopus laevis Noggin4 cannot antagonise BMP signalling; instead, it specifically binds to Wnt8 and inhibits the Wnt/β -catenin pathway. Live imaging demonstrated that Noggin4 diffusivity in embryonic tissues significantly exceeded that of other Noggins. Using the Fluorescence Recovery After Photobleaching (FRAP) assay and mathematical modelling, we directly estimated the affinity of Noggin4 for Wnt8 in living embryos and determined that Noggin4 fine-tune the Wnt8 posterior-to-anterior gradient. Our results suggest a role for Noggin4 as a unique, freely diffusing, long-range inhibitor of canonical Wnt signalling, thus explaining its ability to promote head development.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
authors.forename: Fedor M
authors.initials: FM
authors.lastname: Eroshkin
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie gory, 1/40, 119991 Moscow, Russia.
authors.forename: Alexey M
authors.initials: AM
authors.lastname: Nesterenko
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Borodulin
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
authors.forename: Natalia Yu
authors.initials: NY
authors.lastname: Martynova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Ermakova
authors.affiliation: Institute of Protein Research, Russian Academy of Sciences, Pushchino, 142290 Moscow Region, Russia.
authors.forename: Fatima K
authors.initials: FK
authors.lastname: Gyoeva
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
authors.forename: Eugeny E
authors.initials: EE
authors.lastname: Orlov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Belogurov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Lukyanov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Bayramov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
authors.forename: Andrey G
authors.initials: AG
authors.lastname: Zaraisky
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D018507:Gene Expression Regulation, Developmental; D006257:Head / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D017403:In Situ Hybridization; D007700:Kinetics; D018613:Microscopy, Confocal; D008962:Models, Theoretical; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics* / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C000613514:Noggin4 protein, Xenopus laevis; D051153:Wnt Proteins; D029867:Xenopus Proteins; C495248:wnt8a protein, Xenopus