title: Axis Patterning by BMPs: Cnidarian Network Reveals Evolutionary Constraints.
abstract: BMP signaling plays a crucial role in the establishment of the dorso-ventral body axis in bilaterally symmetric animals. However, the topologies of the bone morphogenetic protein (BMP) signaling networks vary drastically in different animal groups, raising questions about the evolutionary constraints and evolvability of BMP signaling systems. Using loss-of-function analysis and mathematical modeling, we show that two signaling centers expressing different BMPs and BMP antagonists maintain the secondary axis of the sea anemone Nematostella. We demonstrate that BMP signaling is required for asymmetric Hox gene expression and mesentery formation. Computational analysis reveals that network parameters related to BMP4 and Chordin are constrained both in Nematostella and Xenopus, while those describing the BMP signaling modulators can vary significantly. Notably, only chordin, but not bmp4 expression needs to be spatially restricted for robust signaling gradient formation. Our data provide an explanation of the evolvability of BMP signaling systems in axis formation throughout Eumetazoa.
authors.affiliation: Department for Molecular Evolution and Development, Centre of Organismal Systems Biology, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Grigory
authors.initials: G
authors.lastname: Genikhovich
authors.affiliation: Department for Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland; Swiss Institute of Bioinformatics, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Fried
authors.affiliation: Department for Molecular Evolution and Development, Centre of Organismal Systems Biology, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: M Mandela
authors.initials: MM
authors.lastname: Prünster
authors.affiliation: Department for Molecular Evolution and Development, Centre of Organismal Systems Biology, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Schinko
authors.affiliation: Department for Molecular Evolution and Development, Centre of Organismal Systems Biology, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Anna F
authors.initials: AF
authors.lastname: Gilles
authors.affiliation: Department for Molecular Evolution and Development, Centre of Organismal Systems Biology, University of Vienna, Althanstraße 14, 1090 Vienna, Austria; Computational Biology Unit, University of Bergen, Thormøhlensgt. 55, 5008 Bergen, Norway.
authors.forename: David
authors.initials: D
authors.lastname: Fredman
authors.affiliation: Department for Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Meier
authors.affiliation: Department for Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland; Swiss Institute of Bioinformatics, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Iber
authors.affiliation: Department for Molecular Evolution and Development, Centre of Organismal Systems Biology, University of Vienna, Althanstraße 14, 1090 Vienna, Austria. Electronic address: ulrich.technau@univie.ac.at.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Technau