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

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dc.contributor.authorZiegler, Berenice
dc.contributor.authorYiallouros, Irene
dc.contributor.authorTrageser, Benjamin
dc.contributor.authorKumar, Sumit
dc.contributor.authorMercker, Moritz
dc.contributor.authorKling, Svenja
dc.contributor.authorFath, Maike
dc.contributor.authorWarnken, Uwe
dc.contributor.authorSchnölzer, Martina
dc.contributor.authorHolstein, Thomas W.
dc.contributor.authorHartl, Markus
dc.contributor.authorMarciniak-Czochra, Anna
dc.contributor.authorStetefeld, Jörg
dc.contributor.authorStöcker, Walter
dc.contributor.authorÖzbek, Suat
dc.date.accessioned2021-07-01T04:12:05Z
dc.date.issued2021-06-09
dc.date.updated2021-07-01T04:12:06Z
dc.description.abstractAbstract 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.
dc.identifier.citationBMC Biology. 2021 Jun 09;19(1):120
dc.identifier.urihttps://doi.org/10.1186/s12915-021-01046-9
dc.identifier.urihttp://hdl.handle.net/1993/35720
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderThe Author(s)
dc.titleThe Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra
dc.typeJournal Article
local.author.affiliationFaculty of Scienceen_US
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