Periodic Reporting for period 2 - HydraMechanics (Mechanical Aspects of Hydra Morphogenesis)
Période du rapport: 2020-08-01 au 2022-01-31
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 the temporal and spatial domains, lead from local molecular 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. My research explores the less-studied mechanical aspects of this problem, focusing on the dynamics of the morphogenesis process at the level of cells and tissues, rather than on its molecular basis. A phenomenological description of morphogenesis at this level is necessarily a gross simplification of the problem. Nevertheless, we believe that such a coarse-grained approach complements traditional studies of morphogenesis that emphasize genetic networks and protein interactions, and will be essential for formulating an integrated, physical view of the morphogenesis process.
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. Hydra provides an excellent model system to pursue this direction, thanks to its exquisite regeneration flexibility and relative simplicity; a regenerating Hydra can be controlled and manipulated, much like a physical system, yet it contains and operates all the machinery required for the development of a viable behaving organism. Using this relatively simple model system, we address fundamental questions regarding the role of mechanics in morphogenesis that are difficult to tackle in more complicated model organisms. Importantly, the basic mechanisms involved, including mechanical interactions between cells and structural reorganization of the actomyosin cytoskeleton in response to mechanical signals, 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. As such, our research on Hydra regeneration will provide an important step towards the integration of mechanics with other developmental processes into a unified biophysical framework of morphogenesis.
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. Hydra provides an excellent model system to pursue this direction, thanks to its exquisite regeneration flexibility and relative simplicity; a regenerating Hydra can be controlled and manipulated, much like a physical system, yet it contains and operates all the machinery required for the development of a viable behaving organism. Using this relatively simple model system, we address fundamental questions regarding the role of mechanics in morphogenesis that are difficult to tackle in more complicated model organisms. Importantly, the basic mechanisms involved, including mechanical interactions between cells and structural reorganization of the actomyosin cytoskeleton in response to mechanical signals, 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. As such, our research on Hydra regeneration will provide an important step towards the integration of mechanics with other developmental processes into a unified biophysical framework of morphogenesis.
The central part of our work during this period focused on the organization of the parallel array of supra-cellular 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 co-localize 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. Based on this work we suggest that the nematic orientation field acts as a “mechanical morphogen”, which in conjugation with other biochemical and physical morphogens directs the pattern formation in regenerating Hydra.
Given our results showing the importance of nematic topological defects in the regeneration process, we are developing and employing sophisticated imaging and analysis tools to characterize the tissue dynamics and cell movements in regenerating Hydra tissues, and correlating them with the nematic actin fiber organization. We further plan to apply mechanical perturbations using various micromanipulation techniques and study whether applied forces can influence the morphological outcome of regenerating Hydra. Altogether, this work will provide an important step toward understanding how the organization of the actomyosin cytoskeleton and the forces it generates, in conjunction with biochemical signaling processes, give rise to the emergence of form in regenerating Hydra, and inspire the development of predictive theoretical models of the morphogenesis process based on active matter physics.