PT - JOURNAL ARTICLE AU - Taishi Kakizuka AU - Yusuke Hara AU - Yusaku Ohta AU - Asuka Mukai AU - Aya Ichiraku AU - Yoshiyuki Arai AU - Taro Ichimura AU - Takeharu Nagai AU - Kazuki Horikawa TI - Cellular logics bringing the symmetry breaking in spiral nucleation revealed by trans-scale imaging AID - 10.1101/2020.06.29.176891 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.06.29.176891 4099 - http://biorxiv.org/content/early/2020/06/29/2020.06.29.176891.short 4100 - http://biorxiv.org/content/early/2020/06/29/2020.06.29.176891.full AB - The spiral wave is a commonly observed spatio-temporal order in diverse signal relaying systems. Although properties of generated spirals have been well studied, the mechanisms for their spontaneous generation in living systems remain elusive. By the newly developed imaging system for trans-scale observation of the intercellular communication among ∼130,000 cells of social amoeba, we investigated the onset dynamics of cAMP signaling and identified mechanisms for the self-organization of the spiral wave at three distinct scalings: At the population-level, the structured heterogeneity of excitability fragments traveling waves at its high/low boundary, that becomes the generic source of the spiral wave. At the cell-level, both the pacemaking leaders and pulse-amplifying followers regulate the heterogeneous growth of the excitability. At the intermediate-scale, the essence of the spontaneous wave fragmentation is the asymmetric positioning of the pacemakers in the high-excitability territories, whose critical controls are operated by a small number of cells, pulse counts, and pulse amounts.Competing Interest StatementThe authors have declared no competing interest.