On the conflict between precision and robustness in the proportion regulation of cell types

In Dictyostelium discoideum the proportion of cell types is known to be actively regulated, recovering, for example, after the removal of a given cell type. However, we have recently shown that regulation is intrinsically imprecise: it controls the proportion above/below certain upper and lower thresholds, but not within an allowed range of values that these thresholds define. To explain this finding we present a model based on (i) a global negative feedback, and (ii) a cell-autonomous positive feedback leading to a hysteresis-like behaviour (i.e, a bistability of cell type). The simulated cell-type proportion is indeed found to span a range of values as a consequence of the bistability. We conclude that there is a general conflict between the precision of proportion regulation and the robustness of the differentiation of cell types.