%0 Journal Article
%A Ziegler, Berenice
%A Yiallouros, Irene
%A Trageser, Benjamin
%A Kumar, Sumit
%A Mercker, Moritz
%A Kling, Svenja
%A Fath, Maike
%A Warnken, Uwe
%A Schnölzer, Martina
%A Holstein, Thomas W
%A Hartl, Markus
%A Marciniak-Czochra, Anna
%A Stetefeld, Jörg
%A Stöcker, Walter
%A Özbek, Suat
%T The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra.
%J BMC biology
%V 19
%N 1
%@ 1741-7007
%C Heidelberg
%I Springer
%M DKFZ-2021-01293
%P 120
%D 2021
%X The Hydra head organizer acts as a signaling center that initiates and maintains the primary body axis in steady state polyps and during budding or regeneration. Wnt/beta-Catenin signaling functions as a primary cue controlling this process, but how Wnt ligand activity is locally restricted at the protein level is poorly understood. Here we report a proteomic analysis of Hydra head tissue leading to the identification of an astacin family proteinase as a Wnt processing factor.Hydra astacin-7 (HAS-7) is expressed from gland cells as an apical-distal gradient in the body column, peaking close beneath the tentacle zone. HAS-7 siRNA knockdown abrogates HyWnt3 proteolysis in the head tissue and induces a robust double axis phenotype, which is rescued by simultaneous HyWnt3 knockdown. Accordingly, double axes are also observed in conditions of increased Wnt activity as in transgenic actin::HyWnt3 and HyDkk1/2/4 siRNA treated animals. HyWnt3-induced double axes in Xenopus embryos could be rescued by coinjection of HAS-7 mRNA. Mathematical modelling combined with experimental promotor analysis indicate an indirect regulation of HAS-7 by beta-Catenin, expanding the classical Turing-type activator-inhibitor model.We show the astacin family protease HAS-7 maintains a single head organizer through proteolysis of HyWnt3. Our data suggest a negative regulatory function of Wnt processing astacin proteinases in the global patterning of the oral-aboral axis in Hydra.
%K Astacin (Other)
%K Axis formation (Other)
%K Hydra (Other)
%K Proteinase (Other)
%K Wnt signaling (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34107975
%R 10.1186/s12915-021-01046-9
%U https://inrepo02.dkfz.de/record/169159