Spatio-temporal Coordination of Active Deformation Forces and Wnt / Hippo-Yap Signaling inHydraRegeneration

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.

Topology changes of the regeneratingHydradefine actin nematic defects as mechanical organizers of morphogenesis

“…How the mechanical role of actin topological defects is coupled to the Wnt organizer remains to be explored. However, recent findings propose that stretching of cells associated with larger stresses at the defects may be coupled to Wnt production through mechano-sensing signalling 22 in line with past findings suggesting a tight coupling mechanochemical coupling in the animal 8,9,23 .…”

Mechanochemical dynamics of collective cells and hierarchical topological defects in multicellular lumens

“…In this work, the simplified Schnakenberg model is used to describe the upstream biochemical signaling network. It is imperative to recognize that the intracellular signaling pathways [e.g., multitiered reaction networks ( 43 , 72 )] and their intercellular propagation [e.g., directional distributions influenced by tissue polarity ( 23 , 73 )] exhibit a level of intricacy beyond the scope of the Schnakenberg model. For the mechanical components, the way how cells contract or are stretched varies across different systems, encompassing the behaviors such as overall volume change ( 61 ), the maintenance of nearly constant volume ( 18 ), or deformations of the basal surface ( 74 ).…”

“…A wide spectrum of intercellular wave patterns, both temporal and spatial, have been identified in multicellular systems spanning various biochemical intricacies ( 13 , 18 – 23 ). In morphogenesis of murine cochlear duct, extracellular signal–regulated kinase (ERK) activation waves have been found to control cell migration and result in the duct elongation ( Fig.…”

“…1D ) ( 20 ). Furthermore, numerous other signaling pathways, such as Wnt ( 23 ), Notch ( 16 ), and Ca 2+ signals ( 21 , 24 ), behave as system-wide wave-shaped regulators that play crucial roles in tissue morphogenesis. While the upstream biochemical messengers may differ between different systems, a common hallmark in these systems is the occurrence of downstream mechanical responses.…”

Mechanical strain focusing at topological defect sites in regenerating Hydra

“…Indeed, local activation of Wnt can promote head organizer formation (Wang et al, 2020) and global Wnt activation results in a multi-headed phenotype (Broun et al, 2005;Ferenc et al, 2021). More recent work revealed that the Hippo-YAP pathway is also involved in axial patterning in Hydra, during budding (Broun et al, 2022) and regeneration from tissue segments and aggregates (Suzuki et al, 2023). Despite this progress, axial patterning in Hydra is still not well understood (Holstein, 2022).…”