β-Catenin and canonical Wnts control two separate pattern formation systems inHydra: Insights from mathematical modelling

Formation of the body axes and the subsequent formation of the apical termini are two fundamental steps during animal development. InHydra, nuclearβ-Catenin and canonical HyWnt3 were identified as major players active in both processes. Based on molecular knowledge of canonical Wnt signaling directly linking nuclearβ-Catenin and HyWnt3 activity, it was frequently assumed thatde novoaxis formation and the head formation were part of the same pattern formation system. In this work, combining new model simulations with available experimental results, we demonstrate that nuclearβ-Catenin and HyWnt3 most likely contribute to two separate de novo pattern formation systems inHydra, organizing development and differentiation on two different spatial scales. In particular, our results suggest that the nuclearβ-Catenin acts on the scale of the whole body, controlling axis formation, whereas canonical HyWnt3 signaling is involved in a downstream pathway responsible for small-scale patterning of the head. Consequently, also in other animals where axis formation was ascribed to canonical Wnt signaling, the underlying mechanisms may be more complex than previously assumed.