Cell- and tissue mechanics in zebrafish germ layer formation

The first major morphogenetic process in the development of most multi-cellular organisms is gastrulation when the three germ layers (ectoderm, mesoderm and endoderm) are formed. While the molecular and cellular mechanisms underlying germ layer progenitor cell fate specification have been intensively studied, the processes by which progenitor specification is translated into the morphogenetic processes triggering germ layer formation are still only poorly understood. In this project, I will use an interdisciplinary approach to elucidate how differences in the molecular, cellular and biophysical properties between the three progenitor cell types control progenitor cell segregation and germ layer formation during zebrafish gastrulation. Recent observations suggest an important role of differential germ layer tissue surface tension in germ layer progenitor cell segregation and germ layer formation during gastrulation. Both adhesive and mechanical progenitor cell properties have been implicated in regulating germ layer tissue surface tension. However, it remains unclear how differences in progenitor cell mechanical and adhesive properties control differential germ layer tissue surface tension, and how differences in germ layer tissue surface tension control germ layer formation. To address these questions, I will determine i) how single progenitor cell adhesive and mechanical properties control progenitor cell-cell contact formation and contact strength; ii) how progenitor cell-cell contact formation translates into germ layer tissue surface tension; and iii) how differential germ layer tissue tension controls germ layer formation during gastrulation. I expect that these approaches will provide novel and important insight into the molecular, cellular and biophysical mechanisms underlying cell segregation and tissue formation in early vertebrate development.

Multi-cellular organisms rely on complex cellular interactions to establish tissues with distinct functional properties. While certain types of cells form tightly adhesive structures as observed in the epithelial layer of the skin or the gastrointestinal tract, other cell types are highly dynamic and can actively migrate to distant locations within the body. This movement is essential for various biological processes such as embryonic development, proper immune responses or wound healing and, if reactivated under pathological conditions, can promote serious conditions such as metastasis of tumour cells. In this project we were able to identify a new type of fast amoeboid motility using early zebrafish embryos as a model system. We were able to establish a new set of experimental assays to monitor the emergence of migratory properties under defined culture conditions and within the physiological tissue environment of the developing embryo. This experimental framework allowed us to uncover a simple polarization mechanism that drives the transformation of embryonic cells into highly motile amoeboid cells. This amoeboid motility switch strongly depends on mechanical and contractile properties of the cellular cytoskeleton and was triggered by stochastic changes in cortex architecture when cells were exposed to biochemical stimuli or compressive forces from the 3D environment. We were further able to show that this amoeboid cell transformation occurs in different embryonic cell types suggesting a potential role for various other physiological and pathological conditions in the adult organism. In addition we developed a mathematical framework to describe cell polarization, cell shape and motility characteristics of transformed cells and provided a new model to describe cell migration patterns and migration efficiency for a large class of different cell types. Since migration characteristics of cells are highly conserved between the developing embryo and the adult organism our work provides a new experimental and theoretical framework to study the impact of cell motility for a wide range of physiological processes with potential implications to malignant cell transformations during cancer metastasis.