Control of epithelial cell layer spreading in zebrafish
Final Report Abstract
Development is the process where a single cell (the fertilised embryo) develops into a fully grown organism with a complex shape. The body of an organism is built up from molecules which form cells and groups of cells that from tissues and tissues that assemble together to form the organs in the correct place to make the body of the animal. All these different levels of organisation arise at distinct times during development and grow to give the specific shape and function of each organ in the body. This results in an organism with a head that is different from its tail, its back is different from its front and its left side is different from its right side that is how the organism forms it main body axes. We are interested in how molecules help cells assemble into tissues and how these go on to form the shape of the body. We are specifically interested in this process early on during development as the body axes form. We aimed to understand how molecules help cells assemble into tissues by combining two scientific approaches. Firstly, we use microscopy to study the how the molecules behave in cells to organise themselves into tissues. Secondly, we use laws of physics to build a mathematical model that describes how how this self-organisation happens, not as a collection of molecules and cell but instead as a material. Observations of how molecules behave under the microscope inform us about the physical properties (for example how it might flow as a liquid) of the material that we model. This has the advantage that we can use the model to understand how the behaviour of the developing embryo at large sizes can arise from the behaviour of molecules at very small sizes in a way that is not possible to study under the microscope. Such an approach has proved very successful in the past applying how physical principals affect development. This is a relatively new approach to doing science that helps us answer fundamental questions in developmental biology, like how the main body axes arise, which might prove useful in helping cure developmental diseases. We studied the self-organisation of tissues during development in zebrafish. This is a good model organism to study self organisation because there is a time in development when the first boy axis forms when the movement of cells and tissues can easily be followed using microscopy. Many of the molecules that influence these movements are also known. In our previous grant on this topic we showed that a physical model could describe this process well. Our aim was to perform cell biology experiments, together with our collaborator, to provide data that would let us improve the model. Our most important results are as follows. We showed that the tissue must become more fluid so that it becomes more like a liquid allowing it to spread during body axis formation. For this to happen, cells changed the shape (becoming more round) and made fewer contacts between cells. Secondly, we looked at the level of one protein that is known to make connections between cells (called ZO-1). We could show that the amount of protein in cells is related to the amount of stress in the tissue. This is now cells can detect and respond to the material properties of the tissue. Surprisingly, we did not observe the kind of interactions between molecules that we needed to understand self-organisation during development in zebrafish. Instead we turned to another organism to help build a physical model. To do this we used a nematode called C. elegans as a model organism. C. elegans undergoes also sets its body axes early during development and we could show that there were the right kind of feedback mechanisms between proteins that we could model. We also selected the quail as another model organism to apply physical theory to describe its development. In these two organisms, we could show that our improved physical model could predict the behaviour that we observed during development and showed that physical principals were behind the kind of self organisation that happens there.
Publications
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The Physical Basis of Coordinated Tissue Spreading in Zebrafish Gastrulation. Developmental Cell, 40(4), 354-366.e4.
Morita, Hitoshi; Grigolon, Silvia; Bock, Martin; Krens, S.F. Gabriel; Salbreux, Guillaume & Heisenberg, Carl-Philipp
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Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling. Nature Cell Biology, 21(2), 169-178.
Petridou, Nicoletta I.; Grigolon, Silvia; Salbreux, Guillaume; Hannezo, Edouard & Heisenberg, Carl-Philipp
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Guiding self-organized pattern formation in cell polarity establishment. Nature Physics, 15(3), 293-300.
Gross, Peter; Kumar, K. Vijay; Goehring, Nathan W.; Bois, Justin S.; Hoege, Carsten; Jülicher, Frank & Grill, Stephan W.
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Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow. Cell, 179(4), 937-952.e18.
Schwayer, Cornelia; Shamipour, Shayan; Pranjic-Ferscha, Kornelija; Schauer, Alexandra; Balda, Maria; Tada, Masazumi; Matter, Karl & Heisenberg, Carl-Philipp
