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@ARTICLE{Ziegler:169159,
      author       = {B. Ziegler and I. Yiallouros and B. Trageser and S. Kumar
                      and M. Mercker and S. Kling and M. Fath and U. Warnken$^*$
                      and M. Schnölzer$^*$ and T. W. Holstein and M. Hartl and A.
                      Marciniak-Czochra and J. Stetefeld and W. Stöcker and S.
                      Özbek},
      title        = {{T}he {W}nt-specific astacin proteinase {HAS}-7 restricts
                      head organizer formation in {H}ydra.},
      journal      = {BMC biology},
      volume       = {19},
      number       = {1},
      issn         = {1741-7007},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2021-01293},
      pages        = {120},
      year         = {2021},
      abstract     = {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.},
      keywords     = {Astacin (Other) / Axis formation (Other) / Hydra (Other) /
                      Proteinase (Other) / Wnt signaling (Other)},
      cin          = {B100},
      ddc          = {610},
      cid          = {I:(DE-He78)B100-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34107975},
      doi          = {10.1186/s12915-021-01046-9},
      url          = {https://inrepo02.dkfz.de/record/169159},
}