HydraMechanics · Mechanical Aspects of Hydra Morphogenesis

Morphogenesis is one of the most remarkable examples of biological pattern formation. Despite substantial progress in the field, we still do not understand the organizational principles responsible for the robust convergence of the morphogenesis process, across scales, to form viable organisms under variable conditions. We focus here on the less-studied mechanical aspects of this problem, and aim to uncover how mechanical forces and feedback contribute to the formation and stabilization of the body plan. Regenerating Hydra offer a powerful platform to explore this direction, thanks to their simple body plan, extraordinary regeneration capabilities, and the accessibility and flexibility of their tissues. We propose to follow the regeneration of excised tissue segments, which inherit an aligned supra-cellular cytoskeletal organization from the parent Hydra, as well as cell aggregates, which lack any prior organization. We will employ advanced microscopy techniques and develop elaborate image analysis tools to track cytoskeletal organization and collective cell migration and correlate them with global tissue morphology, from the onset of regeneration all the way to the formation of complete animals. Furthermore, to directly probe the influence of mechanics on Hydra morphogenesis, we propose to apply various mechanical perturbations, and intervene with the axis formation process using external forces and mechanical constraints. Overall, the proposed work seeks to develop an effective phenomenological description of morphogenesis during Hydra regeneration, at the level of cells and tissues, and reveal the mechanical basis of this process. More generally, our research will shed light on the role of mechanics in animal morphogenesis, and inspire new approaches for using external forces to direct tissue engineering and advance regenerative medicine.