title: A novel role of the organizer gene Goosecoid as an inhibitor of Wnt/PCP-mediated convergent extension in Xenopus and mouse.
abstract: Goosecoid (Gsc) expression marks the primary embryonic organizer in vertebrates and beyond. While functions have been assigned during later embryogenesis, the role of Gsc in the organizer has remained enigmatic. Using conditional gain-of-function approaches in Xenopus and mouse to maintain Gsc expression in the organizer and along the axial midline, neural tube closure defects (NTDs) arose and dorsal extension was compromised. Both phenotypes represent convergent extension (CE) defects, arising from impaired Wnt/planar cell polarity (PCP) signaling. Dvl2 recruitment to the cell membrane was inhibited by Gsc in Xenopus animal cap assays and key Wnt/PCP factors (RhoA, Vangl2, Prickle, Wnt11) rescued Gsc-mediated NTDs. Re-evaluation of endogenous Gsc functions in MO-mediated gene knockdown frog and knockout mouse embryos unearthed PCP/CE-related phenotypes as well, including cartilage defects in Xenopus and misalignment of inner ear hair cells in mouse. Our results assign a novel function to Gsc as an inhibitor of Wnt/PCP-mediated CE. We propose that in the organizer Gsc represses CE as well: Gsc-expressing prechordal cells, which leave the organizer first, migrate and do not undergo CE like the Gsc-negative notochordal cells, which subsequently emerge from the organizer. In this model, Gsc provides a switch between cell migration and CE, i.e. cell intercalation.
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Ulmer
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Tingler
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Kurz
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Maerker
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Andre
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Mönch
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Campione
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Deißler
authors.affiliation: Genetics of Vertebrate Development Section, Cancer and Developmental Biology Lab, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Lewandoski
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thumberger
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Schweickert
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University, Jerusalem 9112102, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Fainsod
authors.affiliation: Institute of Human Genetics, University Hospital Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Steinbeißer
authors.affiliation: University of Hohenheim, Garbenstr. 30, 70599 Stuttgart, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Blum
mesh_terms: D000818:Animals; D016764:Cell Polarity; D000072261:Dishevelled Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development; D017930:Genes, Reporter; D051956:Goosecoid Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D020897:Organizers, Embryonic / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*
chemical_list: D000072261:Dishevelled Proteins; D051956:Goosecoid Protein; D051153:Wnt Proteins; D029867:Xenopus Proteins