Collective oscillatory signaling in Dictyostelium discoideum acts as a developmental timer initiated by weak coupling of a noisy pulsatile signal
Christopher A. Brimson, Robert Baines, Elisabeth Sams-Dodd, I. C. Stefanescu, B.A. Evans, Satoshi Kuwana, Hidenori Hashimura, Satoshi Sawai, Christopher R. L. Thompson
Abstract
Oscillatory phenomena play widespread roles in the control of biological systems. In D. discoideum , oscillatory cyclic adenosine monophosphate (cAMP) signaling drives collective behavior and induces a temporal developmental gene expression program. How collective cAMP oscillations emerge or how they encode temporal transcriptional information is still poorly understood. To address this, we identified a transcription factor required for the initiation of collective behavior. Hbx5 activity is cAMP dependent and provides a sensitive single-cell readout for cAMP signaling. Extensive stochastic pulsatile cAMP signaling is found to precede collective oscillations. Stochastic signaling induces Hbx5-dependent transcriptional feedback, which enhances signal sensitivity and cell-cell coupling. This results in the emergence of synchronized collective oscillations, which subsequently activates the GtaC transcription factor and triggers shifts in developmental gene expression. Our results suggest this temporal coordination is encoded by changes in the amplitude of cAMP oscillations and differential sensitivity of these transcription factors to the cAMP-regulated kinase ErkB. • The Hbx5 transcription factor is required for oscillatory collective behavior • Hbx5 subcellular localization is a sensitive single-cell probe for cAMP signaling • Observation of the transition from stochastic to collective oscillatory cAMP signaling • Changes in ErkB oscillations encode a transcriptional developmental timer Brimson et al. explore the emergence of collective cAMP oscillations in Dictyostelium discoideum . They find initial signaling is stochastic but triggers pulsatile transcription factor activation that increases cell-cell excitability, drives the emergence of synchronized collective oscillations, and triggers a temporal developmental gene expression cascade.