Mechano-Chemical Coupling in Hydra Regeneration and Patterning

Abstract

The freshwater cnidarian Hydra can regenerate from wounds, small tissue fragments and even from aggregated cells. This process requires the de novo development of a body axis and oral-aboral polarity, a fundamental developmental process that involves chemical patterning and mechanical shape changes. Gierer and Meinhardt recognized that Hydra’s simple body plan and amenability to in vivo experiments make it an experimentally and mathematically tractable model to study developmental patterning and symmetry breaking. They developed a reaction-diffusion model, involving a short-range activator and a long-range inhibitor, which successfully explained patterning in the adult animal. In 2011, HyWnt3 was identified as a candidate for the activator. However, despite the continued efforts of both physicists and biologists, the predicted inhibitor remains elusive. Furthermore, the Gierer-Meinhardt model cannot explain de novo axis formation in cellular aggregates that lack inherited tissue polarity. The aim of this review is to synthesize the current knowledge on Hydra symmetry breaking and patterning. We summarize the history of patterning studies and insights from recent biomechanical and molecular studies, and highlight the need for continued validation of theoretical assumptions and collaboration across disciplinary boundaries. We conclude by proposing new experiments to test current mechano-chemical coupling models and suggest ideas for expanding the Gierer-Meinhardt model to explain de novo patterning, as observed in Hydra aggregates. The availability of a fully sequenced genome, transgenic fluorescent reporter strains, and modern imaging techniques that enable unprecedented observation of cellular events in vivo, promise to allow the community to crack Hydra’s secret to patterning.

Mechanical characterization of regeneratingHydratissue spheres

“…Although small excised tissue pieces retain axial patterning, it still remains that 1-cellular re-aggregates which cannot conserve either supracellular actin structures or chemical gradients have to show de novo axial patterning during osmotic oscillations, 2-there is evidence of a direct coupling between tissue deformations and Hywnt3 expression (20), one of the most important morphogens involved in Hydra patterning and 3-osmotic oscillations are required for the proper elongation, morphogenesis and regeneration of both excised tissue pieces and cellular re-aggregates. For all these reasons, the focus of the field is currently shifting to an integrated view of Hydra regeneration as a mechano-biological process (26, 30). One clear roadblock to the development of these ideas is our lack of understanding of the rheological properties and mechanical state of regenerating Hydra tissue spheres.…”

Mechanical strain focusing at topological defect sites in regenerating Hydra

“…This model successfully integrated a large body of observations from grafting and regeneration experiments into a coherent picture that has dominated the field, in which tissue-scale gradients of the activator and inhibitor generate short-range activation and long-range inhibition of head formation. Despite its popularity, the mechanistic basis for this model is still unclear, and in particular, the nature of the source term that is a crucial ingredient of the model has remained obscure (Meinhardt, 2012a;Wang et al, 2023b). In the context of our work, it is also important to note that the Gierer-Meinhardt model emphasizes the role of diffusible morphogens, but does not consider the possible contribution of mechanics and the nematic fiber organization to the patterning process (Maroudas-Sacks et al, 2024).…”