Spatiotemporal Coordination of Active Deformation Forces and Wnt / Hippo-Yap Signalling in Hydra Regeneration

There is substantial evidence that Wnt signalling and tissue deformation are key determinants of pattern formation in animals. The coordination of these biochemical and biomechanical spatiotemporal asymmetries is often unknown or controversial. We investigated this relationship by studying regeneration in the freshwater polyp Hydra. In both, reaggregates of dissociated cells and regenerated tissues, we found significant waves of tissue contraction and upregulation of Wnt signalling. Applying a simple mechanical model to the mode analysis of the active deformations, we quantitatively defined the phase reversal of size change and axial deformation in these oscillations as the time point of “biomechanical” body axis formation. Furthermore, modulation of canonical Wnt signalling shifted the timing of this phase reversal. Direct comparison with RNAseq data indicates that “biomechanical” body axis formation occurs only after upregulation of canonical Wnt signalling. Further data suggest that biochemical signalling and mechanical forces synergistically stabilize the body axis and thus subsequent head formation by Hippo-Yap signalling. The bilateral symmetry-breaking mechanism identified here in Hydra most likely represents an evolutionary conserved patterning module from early metazoans to bilaterians.