A negative autoregulation network motif is required for synchronized Myxococcus xanthus development

Abstract

Transcription factor autoregulation is a simple network motif (recurring circuit) built into genetic regulatory networks that direct cell behavior. Negative autoregulation (NAR) network motifs are particularly abundant in bacteria and provide specific functions, such as buffering against transcriptional noise. Here, we investigate the phenotypic consequence of perturbing NAR of a major transcription factor, MrpC, that controls the multicellular development program of the bacterium Myxococcus xanthus. Launch of the developmental program directs certain cells in the population to first aggregate into haystack-shaped mounds, and then to differentiate into environmentally resistant spores to form mature fruiting bodies. Perturbation of MrpC NAR causes a striking phenotype in which cells lose synchronized transition from aggregation to sporulation. Instead, some cells abruptly exit aggregation centers and remain locked in a cohesive swarming state, while the remaining cells transition to spores inside residual fruiting bodies. As predicted, disruption of MrpC NAR led to an increased and broadened population distribution of mrpC expression. Examination of MrpC levels in developmental subpopulations during in situ development demonstrated cells locked in the swarms contained intermediate MrpC levels insufficient to promote sporulation. These results suggest an inherent property of NAR motifs that function in multicellular developmental programs is to facilitate synchronized responses. Significance StatementAll organisms use regulatory networks for cellular homeostasis, mediating appropriate responses to environmental changes, or to direct animal development. Understanding how the basic building blocks (motifs) of regulatory networks contribute to these processes is essential to mitigate the effects of mutations in regulatory networks (i.e. cancers) or to synthesize beneficial organisms. In this study, we demonstrate that a common regulatory motif, a transcription factor that represses its own expression, helps synchronize cells that engage in collective behaviors.