Mechano-logical model of C. elegans germ line suggests feedback on the cell cycle.
Mechano-logical model of C. elegans germ line suggests feedback on the cell cycle.
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DOI：
10.1242/dev.126359
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发表时间：
2015-11-15
期刊：
影响因子：
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通讯作者：
Osborne JM
中科院分区：
文献类型：
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作者：
Atwell K;Qin Z;Gavaghan D;Kugler H;Hubbard EJ;Osborne JM
秀丽隐杆线虫生殖系是研究细胞分裂和分化调控的一个杰出的模式系统。虽然许多调节生殖细胞增殖和命运决定的分子已经被确定，但这些信号如何与细胞动力学和性腺内的物理力量相互作用仍然知之甚少。因此，我们开发了秀丽隐杆线虫生殖系的动态3D计算机模型，结合了细胞之间的机械相互作用和细胞内的决策过程。我们的模型成功地再现了生殖系在发育和成年期间的关键特征，包括合理的排卵率，正确的精子数量，以及生殖系在稳定维持区域的适当组织。该模型强调了一种以前被忽视的方式，即生殖细胞压力可能影响性腺激素的产生，并且还预测成年生殖细胞可能会受到类似于接触抑制的细胞周期的机械反馈。我们提供了与后一种假设相一致的实验数据。最后，我们展示了在模拟过程中记录的细胞轨迹和祖先。本文描述的新方法和软件将力学和细胞决策联系起来，并适用于其他发育和干细胞系统的建模。摘要：秀丽隐杆线虫的三维计算机模型预测，成年生殖细胞在细胞周期中受到类似于接触抑制的机械反馈。
The Caenorhabditis elegans germ line is an outstanding model system in which to study the control of cell division and differentiation. Although many of the molecules that regulate germ cell proliferation and fate decisions have been identified, how these signals interact with cellular dynamics and physical forces within the gonad remains poorly understood. We therefore developed a dynamic, 3D in silico model of the C. elegans germ line, incorporating both the mechanical interactions between cells and the decision-making processes within cells. Our model successfully reproduces key features of the germ line during development and adulthood, including a reasonable ovulation rate, correct sperm count, and appropriate organization of the germ line into stably maintained zones. The model highlights a previously overlooked way in which germ cell pressure may influence gonadogenesis, and also predicts that adult germ cells might be subject to mechanical feedback on the cell cycle akin to contact inhibition. We provide experimental data consistent with the latter hypothesis. Finally, we present cell trajectories and ancestry recorded over the course of a simulation. The novel approaches and software described here link mechanics and cellular decision-making, and are applicable to modeling other developmental and stem cell systems. Summary: A three dimensional in silico model of C. elegans predicts that adult germ cells are subject to a mechanical feedback on the cell cycle akin to contact inhibition.