Funktionelle Charakterisierung neuer molekularer Faktoren bei der Bildung und Erhaltung des Hydra-Kopforganisators
Biochemie
Evolutionäre Zell- und Entwicklungsbiologie der Tiere
Zusammenfassung der Projektergebnisse
Hydra is a basal multicellular organism of the phylum Cnidaria that has long been used as a model organism to study the Spemann-Mangold organizer, an embryonic signalling centre responsible for the formation of the body’s longitudinal axis. The Wnt proteins controlling this process are continually produced in the mouth region of the adult polyp to maintain the body axis. Our main project led to the discovery of the HAS-7 protease that is expressed in a ring-shaped zone separating the head from the body. The transient knockdown of HAS-7 expression resulted in the formation of a second head and body axis as a consequence of increased Wnt signaling. Further biochemical and structural analysis defined HAS-7 as the first Wnt-specific protease of the astacin family. This discovery has important implications for the fields of patterning, developmental biology, evolution, Wnt signaling and proteolytic enzymes. A press release from Heidelberg University featuring the publication in the open access journal BMC Biology can be found here: https://www.uni-heidelberg.de/de/newsroom/neue-erkenntnisse-zur-bildung-derkoerperachse Our extended studies on novel factors involved in organizer formation in cnidarians led to the unexpected discovery of the matricellular protein Thrombospondin as a beta-catenin-regulated molecule, which is expressed from Hydra’s organizer tissues. HmTSP acts as a negative regulator of organizer formation and might be involved in direct Wnt ligand binding or receptor turnover. Overall, the successful completion of the project led to a new future direction in our research: the close interplay between ECM and Wnt-related morphogenesis, which we pictured in a recent review. We plan to analyze the impact of ECM factors on patterning and axis formation in Hydra by a systematic siRNA screen and also include biomechanical aspects in future studies.
Projektbezogene Publikationen (Auswahl)
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Hydra Mesoglea Proteome Identifies Thrombospondin as a Conserved Component Active in Head Organizer Restriction. Sci Rep. 2018 Aug 6;8(1):11753
Lommel M, Strompen J, Hellewell AL, Balasubramanian GP, Christofidou ED, Thomson AR, Boyle AL, Woolfson DN, Puglisi K, Hartl M, Holstein TW, Adams JC and Özbek S
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Emergence of a Thrombospondin Superfamily at the Origin of Metazoans. Mol Biol Evol. 2019 Jun 1;36(6):1220-1238
Shoemark DK, Ziegler B, Watanabe H, Strompen J, Tucker RP, Özbek S and Adams JC
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Extracellular matrix and morphogenesis in cnidarians: a tightly knit relationship. Essays Biochem. 2019 Sep 13;63(3):407-416.
Bergheim BG and Özbek S
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The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra. BMC Biol. 2021 Jun 9;19(1):120
Ziegler B, Yiallouros I, Trageser B, Kumar S, Mercker M, Kling S, Fath M, Warnken U, Schnölzer M, Holstein TW, Hartl M, Marciniak-Czochra A, Stetefeld J, Stöcker W and Özbek S
