Tissue material properties in embryonic development

The project Tissue material properties in embryonic development aims at understanding how the combined activities of molecular and mechanical signals drive embryonic development. The transformation of a single-cell embryo into a fully functional organism has been a long-standing interest not only in the field of developmental biology but also in evolution, biophysics and medicine. Key processes in embryonic development, such as tissue spreading and migration, display conserved features with disease-related processes such as wound healing and tumour metastasis, underlining the importance of studying such processes within the developing organism. Tissue morphogenesis has been described for decades as an outcome of tissue-intrinsic molecular interactions. However, tissue morphogenesis is ultimately brought about by mechanical forces, which must be actively generated, transduced and sensed. The effect force application has on tissue deformation critically depends on the material properties of the tissue - a soft tissue will more easily deform than a stiff tissue. Interestingly, tissues can undergo prompt changes in their material properties, a process that is termed phase transition. The regulation and function of tissue phase transitions in tissue morphogenesis, however, is only little understood. The main hypothesis of this project is that phase transitions play a central role in embryonic development. Specifically, I aim at understanding which types of phase transitions different tissues undergo during early embryogenesis using zebrafish as a model system, how these transitions are regulated on a molecular and cellular level, and how they function in embryogenesis. To achieve this, I will take a multidisciplinary approach utilising tools from biophysics, cell biology, developmental biology, genetics and mathematical modelling. I expect that the results of this project will considerably advance our understanding of how molecular and mechanical signals function in concert to drive tissue morphogenesis in embryonic development.

The project "The role of tissue material properties in embryonic development" aimed at understanding how the combined activities of molecular and mechanical signals drive embryonic development. Tissue morphogenesis has been described as an outcome of molecular interactions and mechanical forces. The effect force application has on tissue deformation critically depends on the material properties of the tissue - a soft tissue will more easily deform than a stiff tissue. Interestingly, tissues can undergo prompt changes in their material properties, a process that is termed phase transition. The regulation and function of tissue phase transitions in tissue morphogenesis, however, is only little understood. The main hypothesis of this project was that phase transitions play a central role in embryonic development. Specifically, I aimed at understanding which types of phase transitions different tissues undergo during early embryogenesis using zebrafish as a model system, how these transitions are regulated on a molecular and cellular level, and how they function in embryogenesis. To achieve this, I used a multidisciplinary approach utilizing tools from biophysics, cell biology, developmental biology, genetics and mathematical modeling in collaboration. We performed biophysical measurements of tissue viscosity and found that the blastoderm - the first tissue formed in zebrafish - abruptly loses its viscosity when it starts spreading. This abrupt softening or fluidization of the embryonic tissue resembled the physical phenomenon of phase transitions. Inspired by theoretical frameworks explaining phase transitions in non-living matter, such as ice melting, we explored which cellular parameters can through small changes trigger dramatic changes in tissue viscosity. We identified that if we consider embryonic tissues as networks of cells connected by cell-cell contacts, from which we could measure their connectivity, we can then apply a theoretical framework of phase transitions in the embryo, called rigidity percolation transition. Using this theory, we found that when tissues have connectivity above a critical value, they are rigid - and thus they can not be deformed, whereas below this value they are floppy - and thus they can easily change shape. This theory was further found to consist a powerful predictor of rigidity of several tissue types. In addition, we found that the critical point in connectivity is reached at the onset of zebrafish tissue morphogenesis and is essential for embryonic development. We further identified that this type of tissue phase transitions is regulated in vivo through a spatial and temporal coordination of cell division, cell adhesion and the Planar Cell Polarity molecular pathway. The results of this project considerably advanced our understanding of how molecular and mechanical signals function in concert to drive tissue morphogenesis during embryonic development.