The Wnt-specific Astacin Proteinase HAS-7 Restricts Head Organizer Formation in Hydra

Overview

Journal BMC Biol

Publisher Biomed Central

Specialty Biology

Date 2021 Jun 10

PMID 34107975

Citations 10

Authors

Berenice Ziegler

Irene Yiallouros

Benjamin Trageser

Sumit Kumar

Moritz Mercker

Svenja Kling

Maike Fath

Uwe Warnken

Martina Schnolzer

Thomas W Holstein

Markus Hartl

Anna Marciniak-Czochra

Jorg Stetefeld

Walter Stocker

Suat Ozbek

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

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