RT Journal Article SR Electronic T1 An evolutionary-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra JF bioRxiv FD Cold Spring Harbor Laboratory SP 265785 DO 10.1101/265785 A1 Matthias C. Vogg A1 Leonardo Beccari A1 Laura Iglesias Ollé A1 Christine Rampon A1 Sophie Vriz A1 Chrystelle Perruchoud A1 Yvan Wenger A1 Brigitte Galliot YR 2018 UL http://biorxiv.org/content/early/2018/02/14/265785.abstract AB The Hydra polyp regenerates its head by transforming the gastric tissue below the wound into a head organizer made of two antagonistic cross-reacting components. The activator, previously characterized as Wnt3, drives apical differentiation by acting locally and auto-catalytically. The uncharacterized inhibitor, produced under the control of the activator, prevents ectopic head formation. By crossing RNA-seq data obtained in a β-catenin(RNAi) screen performed in planarians and a quantitative analysis of positional and temporal gene expression in Hydra, we identified Sp5 as a transcription factor that fulfills the head inhibitor properties: a Wnt/β-catenin inducible expression, a graded apical-to-basal expression, a sustained up-regulation during head regeneration, a multi-headed phenotype when knocked-down, a repressing activity on Wnt3 expression. In mammalian cells, Hydra and zebrafish Sp5 repress Wnt3 promoter activity while Hydra Sp5 also auto-activates its expression, possibly via β-catenin and/or Tcf/Lef1 interaction. This work identifies Sp5 as a novel potent feedback loop inhibitor of Wnt/β-catenin signaling across eumetazoans.