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.

中文翻译：

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盘基网柄菌 （Dictyostelium disccoideum） 中的集体振荡信号传导充当由噪声脉动信号的弱耦合启动的发育计时器


振荡现象在生物系统的控制中起着广泛的作用。 在盘状腺苷中，振荡环磷酸腺苷 （cAMP） 信号传导驱动集体行为并诱导时间发育基因表达程序。集体 cAMP 振荡如何出现或它们如何编码时间转录信息仍然知之甚少。为了解决这个问题，我们确定了集体行为启动所需的转录因子。Hbx5 活性是 cAMP 依赖性的，并为 cAMP 信号传导提供灵敏的单细胞读数。发现广泛的随机搏动 cAMP 信号传导先于集体振荡。随机信号转导诱导 Hbx5 依赖性转录反馈，从而增强信号敏感性和细胞间耦合。这导致同步集体振荡的出现，随后激活 GtaC 转录因子并触发发育基因表达的变化。我们的结果表明，这种时间协调是由 cAMP 振荡幅度的变化和这些转录因子对 cAMP 调节的激酶 ErkB 的差异敏感性编码的。