Spatio-temporal Coordination of Active Deformation Forces and Wnt / Hippo-Yap Signaling in Hydra Regeneration

Abstract

Ample evidence suggests that Wnt signaling and tissue deformation are key determinants for pattern formation in animals. The coordination of these biochemical and biomechanical spatio-temporal 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 tissue regenerates, we found significant tissue contraction waves and upregulation of Wnt signaling. 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 those oscillations as the time point of "biomechanical" symmetry breaking. Moreover, overexpression and inhibition of canonical Wnt signaling modulated the timing of this biomechanical symmetry breaking. A direct comparison with the RNAseq data indicates that the biomechanical symmetry breaking occurs only after the upregulation of canonical Wnt signaling. Further data suggest that biochemical signaling and biomechanical active deformation synergistically stabilize the body axis and hence the following head structure formation by Hippo-Yap signaling. The symmetry breaking mechanism identified here in Hydra most likely represents a patterning module that is evolutionary conserved from early metazoan to bilaterian animals.