Journal Article

DKFZ-2021-01293

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.DKFZ* ; Schnölzer, M.DKFZ* ; Holstein, T. W. ; Hartl, M. ; Marciniak-Czochra, A. ; Stetefeld, J. ; Stöcker, W. ; Özbek, S.

2021
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1186/s12915-021-01046-9

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.

Keyword(s): Astacin ; Axis formation ; Hydra ; Proteinase ; Wnt signaling

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Contributing Institute(s):

1. B100 Funktionelle Proteomanalyse (B100)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

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