During Hydra regeneration, supracellular actomyosin fibres are disoriented at two distinct foci of the regenerating tissue. These sites of nematic topological defects eventually form the new head and foot of the regenerated animal. In a new study, Yonit Maroudas-Sacks, Marko Popović, Kinneret Keren and colleagues propose a positive-feedback loop that incorporates fibre organisation, tissue strain and morphogen gradients to promote head organiser formation. To find out more about the work, we caught up with first author Yonit Maroudas-Sacks and co-corresponding author Marko Popović, Group Leader at the Max Planck Institute for the Physics of Complex Systems, Germany.
Yonit Maroudas-Sacks (left) and Marko Popović (right). Image courtesy of the Max Planck Institute for Cell Biology and Genetics, Dresden, Germany.
Marko, can you give us your scientific biography and the questions your lab is trying to answer?
MP: I am a physicist who became interested in biological systems through a summer internship, which then motivated me to choose a PhD position in biological physics. This started to define my interest in exploring biological tissues as complex active materials. Several years ago I met Kinneret Keren, whose group explores the remarkable world of Hydra regeneration, and we started regular discussions that turned into a collaboration between the groups.
A striking combination of simplicity, as Hydra is composed of only two epithelial layers enclosing a lumen, and complexity reflected in regeneration, excitability and topological defects quickly brought the Hydra to the top of my interests. In my group, we aim to understand how complex behaviours of biological tissues can emerge from interactions among simple building blocks, which we pursue both by studying more abstract models from which we hope to extract basic principles, as well as by working closely with experimental groups to understand behaviour of particular biological systems.
Yonit, how did you come to work in the lab and what drives your research today?
YM-S: After studying both physics and biology for my undergraduate degree, and some theoretical biophysics research experience, I was looking for an experimental lab that brings these disciplines together. Initially, I wasn't sure I was interested in the Hydra project, but could immediately see that the group and the PI (Prof. Kinneret Keren) were a good fit for me and that it was a place where I would learn a lot. I quickly became fascinated with the question of how cells and tissues organise into complex functional organisms, and the role that mechanics can play in this process, and I enjoy applying a quantitative and systematic approach to investigating these questions.
What is the background of the field that inspired your work?
MP:Hydra and its regeneration have inspired and puzzled people for a very long time. It is the first system in which the concept of an organiser in development and regeneration was identified. Furthermore, it also motivated the development of famous reaction-diffusion models that influenced the field for decades. Through more recent work, including by the group of Kinneret Keren, it became clear that spatial patterning and activity of the supracellular muscle fibres are important components of Hydra physiology and regeneration, which led to our work.
Hydra and its regeneration have inspired and puzzled people for a very long time
Can you give us the key results of the paper in a paragraph?
MP: In this work, we discovered that regenerating Hydra tissues originating from tissue segments display a characteristic pattern of muscle fibre organisation that contains regions that can be identified as foci of the global organisation pattern. These foci will later become sites of nematic topological defects in the fibre organisation, and ultimately the locations of the morphological features (head and foot) of the regenerated animal. The tissue at these foci undergoes large, repetitive, stretching and rupture events, which can be related to contractions of the muscle fibres, and are most pronounced at the site of the future head of the regenerating Hydra. We propose a positive-feedback loop whereby tissue strain during contraction events enhances local morphogen production at the foci, and fibres, in turn, align with the gradient of radially diffusing morphogen, which positively reinforces local strain focusing at the foci. To explore this further, we have developed a biophysical model, based on a vertex model that incorporates both active stresses as a result of muscle contractions and a morphogen source that is coupled to local tissue strain. This model is able to reproduce the experimentally observed patterns of focused tissue stretching and muscle fibre organisation.
Yonit, when doing the research, did you have any particular result or eureka moment that has stuck with you?
YM-S: In previous work, we had identified the sites of aster-shaped defects in the organisation of the muscle fibres during Hydra regeneration as the sites in which the head would form. I therefore decided to try and image such sites in the tissue at higher magnification and time-resolution than before. The remarkable dynamics of repeated stretching events at the defect sites suddenly became apparent while looking at the movies. In contrast to this, it is interesting how other key results only came to light with careful systematic characterisation. An example of such a result is the fact that there is a striking asymmetry between the deformation patterns observed in the future head and future foot sites from the very onset of regeneration, an observation made by our lab manager, Liora (one of the co-authors), through careful analysis of hundreds of events.
The remarkable dynamics of repeated stretching events at the defect sites suddenly became apparent while looking at the movies
Fibre organisation (left), cellular organisation (centre), and cell areas (right) in the ectoderm of a regenerating Hydra before (top) and at the peak of (bottom) a large stretching event at the future head region. Scale bar: 100 μm.
And what about the flipside: any moments of frustration or despair?
YM-S: At times, the fact that the project required very tight-knit coordination between people in different geographical locations, each of whom faced different challenges and constraints at different times, has been challenging. This includes synchronisation of two collaborating groups, and also the fact that I had actually already left the lab to start my postdoc at the early stages of preparing the manuscript.
Why did you choose to submit this paper to Development?
MP: Two main reasons led us to choose to submit the paper to Development. The first was the feeling that, as a paper that combines theoretical and experimental work, and proposes a hypothesis that is open to future exploration, the journal would provide a good platform to reach the prospective audience we are aiming for. In addition, we believe in the ideology of The Company of Biologists and its contribution to the community, and therefore wanted to support it by choosing this journal.
Yonit, what is next for you after this paper?
YM-S: I am now roughly a year into my postdoc, at the Physics of Life Cluster of Excellence and Max Planck Institute for Cell Biology and Genetics in Dresden, Germany. My project is a collaboration between the groups of Otger Campàs and Jesse Veenvliet, where I am working on the mechanical aspects of early development in zebrafish.
Marko, where will this story take your lab next?
MP: While our work has uncovered the strong colocalisation of mechanical cues, pattern organisation and localisation of the head organiser in Hydra, and proposed that they are related through a positive-feedback loop, it has also opened several new research avenues. In particular, it remains unclear how exactly the proposed feedback loop functions, or what emergent phenomena could be identified theoretically and tested experimentally. Our fruitful collaboration with the group of Kinneret Keren is continuing, with the aim of developing new experimental and data analysis techniques, and biophysical models with which we will explore these questions.
Finally, let's move outside the lab – what do you like to do in your spare time?
YM-S: I love the outdoors and, even though this may sound surprising, I have been enjoying the outdoors (and even the weather!) in Germany and the amazing accessibility to nature. Otherwise, I have a 3-year-old son and generally enjoy spending time with him, and sharing both new and familiar experiences with him and my partner.
Y.M.-S.: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden 01307, Germany.
M.P.: Max-Planck Institute for Physics of Complex Systems, MPI-PKS, Nothnitzer Strasse 38, Dresden 01187, Germany; Cluster of Excellence, Physics of Life, Technische Universitat Dresden, Arnoldstrasse 18, Dresden 01307, Germany; Center for Systems Biology, Pfotenhauerstrasse 108, Dresden 01307, Germany.
E-mail: [email protected]
