TY  - JOUR
AU  - Ziegler, Berenice
AU  - Yiallouros, Irene
AU  - Trageser, Benjamin
AU  - Kumar, Sumit
AU  - Mercker, Moritz
AU  - Kling, Svenja
AU  - Fath, Maike
AU  - Warnken, Uwe
AU  - Schnölzer, Martina
AU  - Holstein, Thomas W
AU  - Hartl, Markus
AU  - Marciniak-Czochra, Anna
AU  - Stetefeld, Jörg
AU  - Stöcker, Walter
AU  - Özbek, Suat
TI  - The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra.
JO  - BMC biology
VL  - 19
IS  - 1
SN  - 1741-7007
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2021-01293
SP  - 120
PY  - 2021
AB  - 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.
KW  - Astacin (Other)
KW  - Axis formation (Other)
KW  - Hydra (Other)
KW  - Proteinase (Other)
KW  - Wnt signaling (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34107975
DO  - DOI:10.1186/s12915-021-01046-9
UR  - https://inrepo02.dkfz.de/record/169159
ER  -