title: Positioning of the midbrain-hindbrain boundary organizer through global posteriorization of the neuroectoderm mediated by Wnt8 signaling.
abstract: The organizing center located at the midbrain-hindbrain boundary (MHB) patterns the midbrain and hindbrain primordia of the neural plate. Studies in several vertebrates showed that the interface between cells expressing Otx and Gbx transcription factors marks the location in the neural plate where the organizer forms, but it is unclear how this location is set up. Using mutant analyses and shield ablation experiments in zebrafish, we find that axial mesendoderm, as a candidate tissue, has only a minor role in positioning the MHB. Instead, the blastoderm margin of the gastrula embryo acts as a source of signal(s) involved in this process. We demonstrate that positioning of the MHB organizer is tightly linked to overall neuroectodermal posteriorization, and specifically depends on Wnt8 signaling emanating from lateral mesendodermal precursors. Wnt8 is required for the initial subdivision of the neuroectoderm, including onset of posterior gbx1 expression and establishment of the posterior border of otx2 expression. Cell transplantation experiments further show that Wnt8 signaling acts directly and non-cell-autonomously. Consistent with these findings, a GFP-Wnt8 fusion protein travels from donor cells through early neural plate tissue. Our findings argue that graded Wnt8 activity mediates overall neuroectodermal posteriorization and thus determines the location of the MHB organizer.
authors.affiliation: Department of Genetics, University of Technology Dresden, c/o Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Muriel
authors.initials: M
authors.lastname: Rhinn
authors.forename: Klaus
authors.initials: K
authors.lastname: Lun
authors.forename: Marta
authors.initials: M
authors.lastname: Luz
authors.forename: Michaela
authors.initials: M
authors.lastname: Werner
authors.forename: Michael
authors.initials: M
authors.lastname: Brand
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins / Q000378:metabolism; D008636:Mesencephalon / Q000196:embryology* / Q000378:metabolism; D020897:Organizers, Embryonic / Q000502:physiology*; D051857:Otx Transcription Factors; D011506:Proteins / Q000378:metabolism*; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D051857:Otx Transcription Factors; D011506:Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C486024:gbx1 protein, zebrafish; C497662:otx2b protein, zebrafish; C094521:wnt8a protein, zebrafish