The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra
| Autor: | Sumit Kumar, Berenice Ziegler, Markus Hartl, Walter Stöcker, Irene Yiallouros, Jörg Stetefeld, Suat Özbek, Maike Fath, Anna Marciniak-Czochra, Uwe Warnken, Benjamin Trageser, Moritz Mercker, Thomas W. Holstein, Svenja Kling, Martina Schnölzer |
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| Přispěvatelé: | University of Manitoba |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Physiology Hydra QH301-705.5 Xenopus Plant Science Proteinase General Biochemistry Genetics and Molecular Biology Structural Biology Astacin Axis formation Animals RNA Small Interfering Biology (General) Wnt Signaling Pathway Ecology Evolution Behavior and Systematics Actin beta Catenin Body Patterning Gene knockdown Budding biology Regeneration (biology) Wnt signaling pathway Metalloendopeptidases Cell Biology biology.organism_classification Wnt signaling Cell biology Wnt Proteins Proteolysis Lernaean Hydra General Agricultural and Biological Sciences Head Developmental Biology Biotechnology Research Article |
| Zdroj: | BMC Biology, Vol 19, Iss 1, Pp 1-22 (2021) BMC Biology |
| ISSN: | 1741-7007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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