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100 1 _ |a Ziegler, Berenice
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245 _ _ |a The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra.
260 _ _ |a Heidelberg
|c 2021
|b Springer
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520 _ _ |a 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.
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650 _ 7 |a Astacin
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650 _ 7 |a Axis formation
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650 _ 7 |a Hydra
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650 _ 7 |a Proteinase
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650 _ 7 |a Wnt signaling
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700 1 _ |a Yiallouros, Irene
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700 1 _ |a Trageser, Benjamin
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700 1 _ |a Kumar, Sumit
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700 1 _ |a Mercker, Moritz
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700 1 _ |a Kling, Svenja
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700 1 _ |a Fath, Maike
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700 1 _ |a Warnken, Uwe
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700 1 _ |a Schnölzer, Martina
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700 1 _ |a Holstein, Thomas W
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700 1 _ |a Hartl, Markus
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700 1 _ |a Marciniak-Czochra, Anna
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700 1 _ |a Stetefeld, Jörg
|b 12
700 1 _ |a Stöcker, Walter
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700 1 _ |a Özbek, Suat
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773 _ _ |a 10.1186/s12915-021-01046-9
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