β-catenin and canonical Wnts in Hydra pattern formation: Insights from mathematical modelling into two distinct systems

Formation of the body axes and the subsequent formation of the apical termini are fundamental steps during animal development. Nuclear β-catenin and canonical Wnt3 have been identified as major players in both these processes in Hydra. Based on molecular knowledge of canonical Wnt signalling directly linking nuclear β-catenin and Wnt3 activity, de novo axis formation and head formation have frequently been assumed to be part of the same pattern formation system. In this study, we investigated this relationship by combining new model simulations with available experimental results. We demonstrated that nuclear β-catenin and Wnt3 likely contribute to two distinct de novo pattern formation systems in Hydra, organizing development and differentiation on two different spatial scales. In particular, the results suggested that nuclear β-catenin acts at the scale of the whole body to control axis formation, whereas canonical Wnt3 signalling is involved in a downstream pathway responsible for small-scale patterning of the head. These results suggest that the underlying mechanisms may also be more complex than previously assumed in other animals where axis formation has been ascribed to canonical Wnt signalling.