title: Autoregulatory and repressive inputs localize Hydra Wnt3 to the head organizer.
abstract: Polarized Wnt signaling along the primary body axis is a conserved property of axial patterning in bilaterians and prebilaterians, and depends on localized sources of Wnt ligands. However, the mechanisms governing the localized Wnt expression that emerged early in evolution are poorly understood. Here we find in the cnidarian Hydra that two functionally distinct cis-regulatory elements control the head organizer-associated Hydra Wnt3 (HyWnt3). An autoregulatory element, which mediates direct inputs of Wnt/β-catenin signaling, highly activates HyWnt3 transcription in the head region. In contrast, a repressor element is necessary and sufficient to restrict the activity of the autoregulatory element, thereby allowing the organizer-specific expression. Our results reveal that a combination of autoregulation and repression is crucial for establishing a Wnt-expressing organizing center in a basal metazoan. We suggest that this transcriptional control is an evolutionarily old strategy in the formation of Wnt signaling centers and metazoan axial patterning.
authors.affiliation: Department of Molecular Evolution and Genomics, Heidelberg Institute of Zoology, University of Heidelberg, D-69120 Heidelberg, Germany. nakamura@zoo.uni-heidelberg.de
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Charisios D
authors.initials: CD
authors.lastname: Tsiairis
authors.forename: Suat
authors.initials: S
authors.lastname: Özbek
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Holstein
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D017353:Gene Deletion; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006829:Hydra / Q000235:genetics*; D008024:Ligands; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D051176:beta Catenin / Q000378:metabolism
chemical_list: D008024:Ligands; D012333:RNA, Messenger; D051153:Wnt Proteins; D060508:Wnt3 Protein; D051176:beta Catenin; D049452:Green Fluorescent Proteins