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BMC Biol 2021 Jun 09;191:120. doi: 10.1186/s12915-021-01046-9.
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The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra.

Ziegler B , Yiallouros I , Trageser B , Kumar S , Mercker M , Kling S , Fath M , Warnken U , Schnölzer M , Holstein TW , Hartl M , Marciniak-Czochra A , Stetefeld J , Stöcker W , Özbek S .

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.

PubMed ID: 34107975
Article link: BMC Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: pdlim3 wnt3 wnt8a
GO keywords: axis specification [+]

Phenotypes: Xla Wt + Hvu.wnt3 (Fig.4.C) [+]

Article Images: [+] show captions
References [+] :
Adams, The genome sequence of Drosophila melanogaster. 2000, Pubmed