The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra

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 p...

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Published in:	BMC biology Vol. 19; no. 1; p. 120
Main Authors:	Ziegler, Berenice, Yiallouros, Irene, Trageser, Benjamin, Kumar, Sumit, Mercker, Moritz, Kling, Svenja, Fath, Maike, Warnken, Uwe, Schnölzer, Martina, Holstein, Thomas W, Hartl, Markus, Marciniak-Czochra, Anna, Stetefeld, Jörg, Stöcker, Walter, Özbek, Suat
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 09-06-2021 BioMed Central BMC
Subjects:	Actin Alternation learning Analysis Animals Astacin Axes (reference lines) Axis formation beta Catenin - genetics beta Catenin - metabolism Body Patterning Coinjection Embryos Enzymes Genetic aspects Genetic engineering Head Hydra Hydra - genetics Identification and classification Ligands Mass spectrometry Mathematical models Metalloendopeptidases Methods mRNA Observations Peptides Phenotypes Polyps Polyps (organisms) Proteinase Proteins Proteolysis Proteomics Regeneration RNA, Small Interfering Robustness (mathematics) Scientific imaging Signaling siRNA Wnt protein Wnt proteins Wnt Proteins - metabolism Wnt signaling Wnt Signaling Pathway β-Catenin Canada Wnt signaling Astacin Hydra Proteinase Axis formation
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1741-7007 1741-7007
DOI:	10.1186/s12915-021-01046-9