%0 Generic
%A Ziegler, Bérénice Dorothea
%C Heidelberg
%D 2021
%F heidok:30006
%R 10.11588/heidok.00030006
%T A Wnt-specific astacin proteinase restricts head organizer formation in Hydra
%U https://archiv.ub.uni-heidelberg.de/volltextserver/30006/
%X The freshwater polyp Hydra is one of the best model organisms to analyze body axis patterning and organizer formation. Hydra possesses only one radial-symmetric body axis, which is established and maintained by autocatalytical Wnt/β-catenin signaling in the head organizer. Constant environmental influence, cell flow, as well as injury response can lead to an upregulation of Wnt/β-catenin signaling. A mechanism to restrict Wnt/β-catenin signaling is necessary to ensure the dominance of a single body axis and suppress the formation of ectopic axes and multiple head organizers. So far, only the transcription factor Sp5 (Vogg et al. 2019) has been described as a repressor of Wnt/β-catenin signaling in Hydra. Which factors restrict the activity of secreted Wnt ligands at the protein level has been elusive.  In this study, 11 novel Hydra astacin metalloproteases (HAS-1 to -11) are described, which were discovered by a secretome analysis for factors showing a proteolytic activity on HyWnt3. All Hydra astacins showed a transcriptional profile in endodermal gland cells and either exhibited a ring-like expression pattern under the head region or a graded expression pattern peaking at the tentacle base.   HAS-7 was identified to be a promising candidate to restrict HyWnt3 at the protein level, as HAS-7 RNAi induced ectopic axis formation in Hydra. Importantly, HAS-7 was sufficient to revert double axis formation induced by HyWnt3 mRNA in Xenopus laevis embryos. An indirect regulation of HAS-7 by Wnt/β-catenin signaling was established by experimental promoter analysis and validated by mathematical modelling.  In summary, this work introduces HAS-7 as a negative regulator of HyWnt3 in the classical sense of the Gierer-Meinhardt activator-inhibitor model, and therefore plays an important role in Hydra axis formation and maintenance.