On the role of mechanical feedback in synchronous to asynchronous transition during embryogenesis

Abdul Malmi-Kakkada, Sumit Sinha, D. Thirumalai
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Abstract

Experiments have shown that during the initial stage of Zebrafish morphogenesis a synchronous to asynchronous transition (SAT) occurs, as the cells divide extremely rapidly. In the synchronous phase, the cells divide in unison unlike in the asynchronous phase. Despite the widespread observation of SAT in experiments, a theory to calculate the critical number of cell cycles, $n^{*}$, at which asynchronous growth emerges does not exist. Here, using a model for the cell cycle, with the assumption that cell division times are Gaussian distributed with broadening, we predict $n^{*}$ and the time at which the SAT occurs. The theoretical results are in excellent agreement with experiments. The theory, supplemented by agent based simulations, establish that the SAT emerges as a consequence of biomechanical feedback on cell division. The emergence of asynchronous phase is due to linearly increasing fluctuations in the cell cycle times with each round of cell division. We also make several testable predictions, which would further shed light on the role of biomechanical feedback on the growth of multicellular systems.
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机械反馈在胚胎发生过程中同步向异步转变中的作用
实验表明,在斑马鱼形态发生的初始阶段,由于细胞分裂极快,发生了同步到异步转变(SAT)。在同步阶段,细胞分裂不像在异步阶段。尽管在实验中对sat进行了广泛的观察,但计算细胞周期临界数的理论,$n^{*}$,并不存在异步生长出现的理论。在这里,使用细胞周期模型,假设细胞分裂时间是高斯分布的,随着展宽,我们预测了$n^{*}$和SAT发生的时间。理论结果与实验结果非常吻合。该理论,辅以基于代理的模拟,确立了SAT作为细胞分裂的生物力学反馈的结果而出现。异步期的出现是由于每一轮细胞分裂时细胞周期时间的波动呈线性增加。我们还做了几个可测试的预测,这将进一步阐明生物力学反馈在多细胞系统生长中的作用。
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