Memory and modularity in cell-fate decision making

Genetically identical cells sharing an environment can display markedly different phenotypes. It is often unclear how much of this variation derives from chance, external signals, or attempts by individual cells to exert autonomous phenotypic programs. By observing thousands of cells for hundreds of consecutive generations under constant conditions, we dissect the stochastic decision between a solitary, motile state and a chained, sessile state in Bacillus subtilis. We show that the motile state is ‘memoryless’, exhibiting no autonomous control over the time spent in the state. In contrast, the time spent as connected chains of cells is tightly controlled, enforcing coordination among related cells in the multicellular state. We show that the three-protein regulatory circuit governing the decision is modular, as initiation and maintenance of chaining are genetically separable functions. As stimulation of the same initiating pathway triggers biofilm formation, we argue that autonomous timing allows a trial commitment to multicellularity that external signals could extend. This study shows that Bacillus subtilis switches from a solitary, motile lifestyle to a multicellular, sessile state in a random, memoryless fashion, but that the underlying gene network is buffered against its own stochastic variation to tightly time the reverse transition; thus bacteria keep track of time to force their progeny to cooperate during the earliest stage of multicellular growth. Genetically identical cells can make different cell-fate decisions in response to explicit extracellular triggers but also as a reaction to apparently stochastic or randomly generated stimuli arising within the cell. Is the underlying noise in gene expression a 'bug' or a key part of the cellular program? This study, a joint project from the labs of Richard Losick and Johan Paulsson, shows that chance has a role, at least for Bacillus subtilis bacteria. B. subtilis cells face a dramatic cell-fate decision, the transition between the solitary, motile state and the multicellular, chained state. The authors find that the bacterium switches from solitary to multicellular states according to a random, memoryless molecular mechanism, but that the underlying gene network is buffered against its own stochastic variations for the reverse transition. Thus bacteria keep track of time in order to force their progeny to cooperate with each other — a process that may inspire similarly quantitative research on development and cancer.