1476-468751575252014Nov06NatureNodal signalling determines biradial asymmetry in Hydra.112115112-510.1038/nature13666In bilaterians, three orthogonal body axes define the animal form, with distinct anterior-posterior, dorsal-ventral and left-right asymmetries. The key signalling factors are Wnt family proteins for the anterior-posterior axis, Bmp family proteins for the dorsal-ventral axis and Nodal for the left-right axis. Cnidarians, the sister group to bilaterians, are characterized by one oral-aboral body axis, which exhibits a distinct biradiality of unknown molecular nature. Here we analysed the biradial growth pattern in the radially symmetrical cnidarian polyp Hydra, and we report evidence of Nodal in a pre-bilaterian clade. We identified a Nodal-related gene (Ndr) in Hydra magnipapillata, and this gene is essential for setting up an axial asymmetry along the main body axis. This asymmetry defines a lateral signalling centre, inducing a new body axis of a budding polyp orthogonal to the mother polyp's axis. Ndr is expressed exclusively in the lateral bud anlage and induces Pitx, which encodes an evolutionarily conserved transcription factor that functions downstream of Nodal. Reminiscent of its function in vertebrates, Nodal acts downstream of β-Catenin signalling. Our data support an evolutionary scenario in which a 'core-signalling cassette' consisting of β-Catenin, Nodal and Pitx pre-dated the cnidarian-bilaterian split. We presume that this cassette was co-opted for various modes of axial patterning: for example, for lateral branching in cnidarians and left-right patterning in bilaterians.WatanabeHiroshiHDepartment of Molecular Evolution and Genomics, Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.SchmidtHeiko AHACenter for Integrative Bioinformatics Vienna (CIBIV), Max F. Perutz Laboratories (MFPL), University of Vienna/Medical University of Vienna, 1030 Vienna, Austria.KuhnAnneADepartment of Molecular Evolution and Genomics, Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.HögerStefanie KSKDepartment of Molecular Evolution and Genomics, Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.KocagözYigitYDepartment of Molecular Evolution and Genomics, Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.Laumann-LippNicoNDepartment of Molecular Evolution and Genomics, Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.OzbekSuatSDepartment of Molecular Evolution and Genomics, Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.HolsteinThomas WTWDepartment of Molecular Evolution and Genomics, Centre for Organismal Studies (COS), Heidelberg University, 69120 Heidelberg, Germany.engJournal ArticleResearch Support, Non-U.S. Gov't20140824