担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

In development, tissue shape changes and gene expression patterns give rise to morphogenesis. Understanding tissue shape changes requires the analysis of mechanical properties of the tissue such as tissue rigidity, cell influx from neighboring tissues, cell shape changes and cell proliferation. Local and global gene expression patterns can be influenced by neighbor exchange and tissue shape changes. Here we review recent studies on the mechanisms for tissue elongation and its influences on dynamic gene expression patterns by focusing on vertebrate somitogenesis. We first introduce mechanical and biochemical properties of the segmenting tissue that drive tissue elongation. Then, we discuss patterning in the presence of cell mixing, scaling of signaling gradients, and dynamic phase waves of rhythmic gene expression under tissue shape changes. We also highlight the importance of theoretical approaches to address the relation between tissue shape changes and patterning.

DOI： 10.1016/j.semcdb.2022.12.009

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bacterial cells maintain their characteristic cell size over many generations. Several rod-shaped bacteria, such as Escherichia coli and the cyanobacteria Synechococcus elongatus, divide after adding a constant length to their length at birth. Through this division control known as the adder mechanism, perturbation in cell length due to physiological fluctuation decays over generations at a rate of 2-1 per cell division. However, previous experiments have shown that the circadian clock in cyanobacteria reduces cell division frequency at a specific time of day under constant light. This circadian gating should modulate the division control by the adder mechanism, but its significance remains unknown. Here we address how the circadian gating affects cell length, doubling time, and cell length stability in cyanobacteria by using mathematical models. We show that a cell subject to circadian gating grows for a long time, and gives birth to elongated daughter cells. These elongated daughter cells grow faster than the previous generation, as elongation speed is proportional to cell length and divide in a short time before the next gating. Hence, the distributions of doubling time and cell length become bimodal, as observed in experimental data. Interestingly, the average doubling time over the population of cells is independent of gating because the extension of doubling time by gating is compensated by its reduction in the subsequent generation. On the other hand, average cell length is increased by gating, suggesting that the circadian clock controls cell length. We then show that the decay rate of perturbation in cell length depends on the ratio of delay in division by the gating τG to the average doubling time τ0 as [Formula: see text] . We estimated τG≈2.5, τ0≈13.6 hours, and τG/τ0≈0.18 from experimental data, indicating that a long doubling time in cyanobacteria maintains the decay rate similar to that of the adder mechanism. Thus, our analysis suggests that the acquisition of the circadian clock during evolution did not impose a constraint on cell size homeostasis in cyanobacteria.

DOI： 10.1016/j.jtbi.2022.111260

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Multiple feedback loops are often found in gene regulations for various cellular functions. In mammalian circadian clocks, oscillations of Period1 (Per1) and Period2 (Per2) expression are caused by interacting negative feedback loops (NFLs) whose protein products with similar molecular functions repress each other. However, Per1 expression peaks earlier than Per2 in the pacemaker tissue, raising the question of whether the peak time difference reflects their different dynamical functions. Here, we address this question by analyzing phase responses of the circadian clock caused by light-induced transcription of both Per1 and Per2 mRNAs. Through mathematical analyses of dual NFLs, we show that phase advance is mainly driven by light inputs to the repressor with an earlier expression peak as Per1, whereas phase delay is driven by the other repressor with a later peak as Per2. Due to the complementary contributions to phase responses, the ratio of light-induced transcription rates between Per1 and Per2 determines the magnitude and direction of phase shifts at each time of day. Specifically, stronger Per1 light induction than Per2 results in a phase response curve (PRC) with a larger phase advance zone than delay zone as observed in rats and hamsters, whereas stronger Per2 induction causes a larger delay zone as observed in mice. Furthermore, the ratio of light-induced transcription rates required for entrainment is determined by the relation between the circadian and light-dark periods. Namely, if the autonomous period of a circadian clock is longer than the light-dark period, a larger light-induced transcription rate of Per1 than Per2 is required for entrainment, and vice versa. In short, the time difference between Per1 and Per2 expression peaks can differentiate their dynamical functions. The resultant complementary contributions to phase responses can determine entrainability of the circadian clock to the light-dark cycle.

DOI： 10.1371/journal.pcbi.1008774

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Integrity of rhythmic spatial gene expression patterns in the vertebrate segmentation clock requires local synchronization between neighboring cells by Delta-Notch signaling and its inhibition causes defective segment boundaries. Whether deformation of the oscillating tissue complements local synchronization during patterning and segment formation is not understood. We combine theory and experiment to investigate this question in the zebrafish segmentation clock. We remove a Notch inhibitor, allowing resynchronization, and analyze embryonic segment recovery. We observe unexpected intermingling of normal and defective segments, and capture this with a new model combining coupled oscillators and tissue mechanics. Intermingled segments are explained in the theory by advection of persistent phase vortices of oscillators. Experimentally observed changes in recovery patterns are predicted in the theory by temporal changes in tissue length and cell advection pattern. Thus, segmental pattern recovery occurs at two length and time scales: rapid local synchronization between neighboring cells, and the slower transport of the resulting patterns across the tissue through morphogenesis.

DOI： 10.7554/eLife.61358

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DOI： 10.1103/PhysRevE.99.062207

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担当区分：筆頭著者,　責任著者  

DOI： 10.1371/journal.pcbi.1006787

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担当区分：責任著者  

DOI： 10.1016/j.semcdb.2018.09.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing Inc.  

DOI： 10.1111/risa.12893

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1103/PhysRevE.96.062210

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jtbi.2017.06.005

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1242/bio.025148

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担当区分：筆頭著者,　責任著者   記述言語：英語  

DOI： 10.1111/dgd.12366

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記述言語：英語  

DOI： 10.1371/journal.pone.0161550

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担当区分：責任著者   記述言語：英語  

DOI： 10.1111/dgd.12262

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/risa.12276

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担当区分：筆頭著者,　責任著者   記述言語：英語  

DOI： 10.1016/j.semcdb.2014.05.011

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bpj.2014.06.011

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1103/PhysRevE.87.032911

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1088/1478-3975/9/3/036006

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記述言語：英語  

DOI： 10.1126/science.1215478

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00285-009-0296-1

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1073/pnas.0907122107

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jtbi.2009.01.003

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11538-007-9230-0

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