How an animal establishes its body axis is a fundamental question in developmental biology. The freshwater cnidarian Hydra is an attractive model for studying axis formation because it is radially symmetric, with a single oral-aboral axis. It was recently proposed that the orientation of the new body axis in a regenerating Hydra polyp is determined by the oral-aboral orientation of the actin-myosin contractile processes (myonemes) in the animal’s outer epithelial layer. However, it remained unclear how the oral-aboral polarity of the body axis would be defined. As Wnt signaling is known to control axis polarity in Hydra and bilaterians, we hypothesized that it plays a role in axis formation during regeneration of Hydra tissue pieces. We tested this hypothesis using pharmacological perturbations and novel grafting experiments to set Wnt signaling and myoneme orientation perpendicular to each other to determine which controls axis formation. Our results demonstrate that Wnt signaling is the dominant encoder of axis orientation and polarity, in line with its conserved role in axial patterning
