Periodic Reporting for period 4 - HydraMechanics (Mechanical Aspects of Hydra Morphogenesis)
Periodo di rendicontazione: 2023-08-01 al 2025-01-31
Morphogenesis is one of the most remarkable examples of biological self-organization. The collective dynamics of numerous building blocks, spanning several orders of magnitude in both space and time, lead from local events to the development of functional multicellular organisms. Understanding how the body plan emerges during morphogenesis is a central question at the forefront of research in developmental biology and biophysics. In our research, we utilize the small predatory animal, Hydra, famous for its extraordinary regeneration capabilities, to study the role of mechanical processes and feedback in morphogenesis. Using this relatively simple model system, we can address fundamental questions that are difficult to tackle in more complicated model organisms.
We use high-resolution live imaging, to follow tissue dynamics and the organization of the supracellular actomyosin fibers in regenerating Hydra. We show that the sites of head and foot formation coincide with the location of nematic topological defects in the orientation of the actin fibers. These sites can be identified from the pattern of inherited actin fibers in regenerating tissue fragments already at the onset of the regeneration process. We find that contractions of the supracellular actomyosin fibers lead to recurring localized tissue stretching and rupture events at these sites. We suggest that these tissue deformations can provide local mechanical cues that spatially focus the various morphogenetic processes involved and promote the robust emergence of morphological features at defect sites. We further employ mechanical constraints to generate frustration that leads to the emergence of excess defects in the regenerating tissue spheroids and show that these perturbations are correlated with the formation of multi-axis animals.
Overall, our results suggest that the nematic organization of the muscle fibers can be considered a “mechanical morphogen” whose dynamics and active-force generation, in conjugation with additional biochemical and biophysical processes, underlies the remarkable self-organization into functional animals during Hydra regeneration. Importantly, the basic mechanisms involved, including mechanochemical feedback and structural reorganization of the actomyosin cytoskeleton, are universal across the animal kingdom. Thus, we expect that the lessons learned from our work will shed light on the mechanical basis of morphogenesis in other organisms, towards the integration of mechanics with other developmental processes into a unified biophysical framework of morphogenesis.
We use high-resolution live imaging, to follow tissue dynamics and the organization of the supracellular actomyosin fibers in regenerating Hydra. We show that the sites of head and foot formation coincide with the location of nematic topological defects in the orientation of the actin fibers. These sites can be identified from the pattern of inherited actin fibers in regenerating tissue fragments already at the onset of the regeneration process. We find that contractions of the supracellular actomyosin fibers lead to recurring localized tissue stretching and rupture events at these sites. We suggest that these tissue deformations can provide local mechanical cues that spatially focus the various morphogenetic processes involved and promote the robust emergence of morphological features at defect sites. We further employ mechanical constraints to generate frustration that leads to the emergence of excess defects in the regenerating tissue spheroids and show that these perturbations are correlated with the formation of multi-axis animals.
Overall, our results suggest that the nematic organization of the muscle fibers can be considered a “mechanical morphogen” whose dynamics and active-force generation, in conjugation with additional biochemical and biophysical processes, underlies the remarkable self-organization into functional animals during Hydra regeneration. Importantly, the basic mechanisms involved, including mechanochemical feedback and structural reorganization of the actomyosin cytoskeleton, are universal across the animal kingdom. Thus, we expect that the lessons learned from our work will shed light on the mechanical basis of morphogenesis in other organisms, towards the integration of mechanics with other developmental processes into a unified biophysical framework of morphogenesis.
The central part of our work focused on the organization of the parallel array of supracellular actin fibers in regenerating Hydra as an active nematic system. Active nematic systems are a class of non-equilibrium systems, composed of elongated objects that consume energy to generate forces, which exhibit a rich spectrum of dynamic behaviors. Such systems are currently under study in different biomimetic systems and in in vitro planar cell layers. In our research, we studied the relation between the large-scale organization of the actin fibers as an active nematic system, and the patterning of the body-plan in regenerating Hydra. We used live imaging to follow the organization of the actin fibers in regenerating Hydra tissues, and showed that the dynamics of the nematic topological defects in the fiber alignment provide an effective characterization of the regeneration process. We found that these topological defects are long-lived and display rich dynamics, including motility as well as merging and annihilation of defect pairs. Importantly, we showed that the nematic topological defects conincide with the sites of formation of functional morphological features in the regenerating animal, allowing us to predict the sites of head and foot formation, long before their appearance, based solely on the organization of the nematic orientation field.
Our work is considered one of the prime examples for the relevance of topological defects to living systems. Our results have been published in papers that appeared in leading journals and was presented in more than 50 talks in scientific meetings and seminars. As part of this project we have implemented and developed sophisticated image analysis tools to characterize the tissue dynamics and cell movements in regenerating Hydra tissues, and correlating them with the nematic actin fiber organization. We have made all these tools publicly available on github. Furthermore, our experimental results have inspired the development of several theoretical models of animal morphogenesis by leading groups worldwide.