From: EMBL

Will give a seminar entitled:

An optimum level of cell cycle heterogeneity determines the onset of morphogenesis

Embryo morphogenesis starts with a transition from cell-autonomous to cell-collective behaviour. Cells, despite operating collectively, are highly heterogeneous in their physiology, raising the question whether cell-level disorder gives embryonic cells the capacity to operate collectively. Here we show that an optimum level of cell cycle heterogeneity drives long-range mechanical coordination to initiate vertebrate morphogenesis. By combining lineage tracking with rigidity percolation theory in zebrafish we show that its first collective behaviour, a rigid-to-floppy tissue phase transition, occurs when cells are most variable in their cell cycle lengths. We identify that variability results from the inheritance of a deterministic hyperbolic growth of the cell cycle length and its noise. The latter is encoded in stochastic differences in resource allocation during cell cleavages due to slight cell size differences between daughter cells. By integrating in vivo and in silico approaches, we solely tune variability without affecting average cell cycle elongation and demonstrate that heterogeneity is the driver of collective tissue fluidization. At an optimum level, the rate of cell cycle-dependent local contact remodelling is stabilizing the tissue close to the critical point of the rigidity transition, at which slight deviations in variability are buffered. However, when cell cycle variability deviates far from its optimum, it plunges the spatiotemporal coordination of the phase transition. Overall, we show that cell-level heterogeneity determines the onset of morphogenesis and that noisy microscopic dynamics are in fact a source of robustness in multicellular systems.

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