%0 Generic
%A Schindler, Magdalena
%C Heidelberg
%D 2026
%F heidok:37091
%R 10.11588/heidok.00037091
%T An Optimum Cell Cycle Heterogeneity Times Tissue Fluidisation at the Onset of Zebrafish Morphogenesis
%U https://archiv.ub.uni-heidelberg.de/volltextserver/37091/
%X Cell-to-cell heterogeneity is present in all biological systems. Whether such heterogeneity is disruption that needs to be controlled, or is actually required for biological processes is subject of debate. For my doctoral work, I focused on the role of heterogeneity in cell cycle dynamics in early embryogenesis. I focused on cell cleavages, reductive cell divisions at the start of embryonic development, that usually desynchronise before the onset of morphogenesis. Although cell cleavage dynamics are regulated at the single cell level, the cell-to-cell desynchronisation observed in early embryos is accompanied with collective behaviour, including shape and pattern formation. In my doctoral work, I addressed the origin and function of heterogeneity in cell cleavages in the onset of zebrafish morphogenesis. Zebrafish morphogenesis is facilitated by tissue fluidization, an abrupt loss in tissue viscosity, driven by cell-cell adhesion remodelling occurring during the cell cleavages. Here, I investigated the importance of variation in cell cycle lengths for tissue fluidization. I dissected (1.) the spatiotemporal dynamics of the cell cycle heterogeneity, and (2.) its origins to eventually (3.) understand its impact on the tissue material state. By using live imaging and quantitative data analysis, I characterised cell cycle dynamics along with tissue material properties using rigidity percolation theory. I detect a super-exponential growth of cell cycle length along with a rapid growth in its variability. As the cell cycle lengthens, its embryo-wide variability peaks, and the tissue undergoes a rigid-to-floppy phase transition at the highest value of variability. Cell cycle manipulations suggest that cell cycle dynamics control this phase transition through regulating the spatiotemporal distribution of cell divisions, that remodel cell-cell contacts. Using theory of stochastic differential equations and simulations of tissue dynamics (in collaboration), along with cell biology experiments, I found that the observed cell cycle dynamics can be explained by inheritance of information from the mother cell to the daughter cells, which is encoded in the cell size differences. Cell size differences may arise due to stochastic division asymmetries and are then propagated throughout each cell lineage. Experimental manipulations of cell size variability allowed me to interfere with only cell cycle variability but not the developmental rate. Such manipulations showed that for tissue fluidisation to robustly occur, an optimal cell size-dependent cell cycle variability is required. Thus, the generation of optimal amounts of biological noise and its propagation through the cell lineage are essential for a robust morphogenetic transition from cell autonomy to the first tissue-scale collective behaviour in this system. Overall, my work uncovers an interplay of coordinated stochastic and deterministic mechanisms of cell cycle dynamics essential for regulating collective tissue properties and morphogenetic robustness.