| Popis: |
Spatial tissue patterning during early morphogenesis depends on the coordinated movement and shape change of tissue cells. Therefore, the identification of the driving forces requires both the quantification of cellular features from image data and computational modelling of tissue dynamics at cellular resolution. Although significant progress has been made in both areas, there are still many unanswered questions. In this work, a mechanochemical simulation framework is applied to model the dynamics of both confluent and non-confluent tissues. First, we review the theory of the topology of epithelial network configurations. Subsequently, we model the self-organization of mesenchymal cells in the nephrogenic niche. Finally, we examine individual aspects of confluent tissue cell mechanics. The following is a brief outline of these investigations. In the first part of this thesis, we investigate how linear relationships between the size and shape of apical cell surfaces arise in epithelia by comparing data and computer modelling with previous explanations. Our results show that, in addition to the known effects of tension and adhesion on cell shape, the size variability of apical cell surfaces is a crucial parameter. Furthermore, our simulations predict that if the size variability of apical cell surfaces is greater than that of most epithelia, this will lead to a nonlinear relationship between size and shape of apical cell surfaces. In the second part of this work, we investigate how mesenchymal cells condense to the adjacent epithelium while swarming through the nephrogenic niche. Although cells are known to switch between adhesive and motile states to coordinate collective processes such as migration or tissue remodelling, it is not yet known how mesenchymal condensation is regulated. Experimental quantifications of mesenchymal cell behaviour and cellular properties reveal a chemokinetic effect of the autocrine factor FGF8, and a computational model of reciprocal signalling between mesenchymal and epithelial cells reproduces the experimentally observed motility gradient and mesenchymal condensation. Moreover, the simulations predict that the balance between mesenchymal and epithelial signalling must be precisely regulated for mesenchymal condensation to occur. The last part of this thesis covers the effect of cell mechanical properties on intercellular contact-dependent signalling and differentiation as well as tissue outgrowth in the primordia of the mouse. |
