The mechanism of shape-dependent stochastic asymmetric cell division

形状依赖性随机不对称细胞分裂的机制

• 批准号: 24770188
• 负责人: AKANUMA Takashi
• 金额: $ 3万
• 依托单位: Nara Institute of Science and Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24770188/
• 关键词: 形; ばらつき; 非対称分裂; 拡散; 国際研究者交流; オランダ; ライブイメージング; 確率; 数理モデル

Cell-to-cell variability is increasingly appreciated as an integral part of biological systems. In this project, we explored how difference in cell shape affects the determination of future cell behavior. In zebrafish embryos, two kinds of V2 interneurons, V2a and V2b are generated from common V2 progenitor cells. It has been suggested that V2 progenitor cells divide along quasi-random directions and there is no cell fate bias at the time of cell division. However we found that varied shapes of V2 progenitor cells are coupled not only to the cell division orientation but also to the binary cell fate determination in a probabilistic manner. We also established an abstract model for shape-dependent stochastic V2 cells' asymmetric division. We analyzed this model by mathematical simulation in silico, and inspected it by manipulating the zebrafish embryos. Our interdisciplinary approach revealed the design principle for the shape-dependent stochastic asymmetric cell division.

细胞间的变异性越来越被认为是生物系统的一个组成部分。在这个项目中，我们探索了细胞形状的差异如何影响未来细胞行为的确定。在斑马鱼胚胎中，两种 V2 中间神经元 V2a 和 V2b 由常见的 V2 祖细胞产生。有人认为V2祖细胞沿着准随机方向分裂，并且细胞分裂时不存在细胞命运偏差。然而，我们发现V2祖细胞的不同形状不仅与细胞分裂方向相关，而且还以概率方式与二元细胞命运决定相关。我们还建立了形状依赖性随机V2细胞不对称分裂的抽象模型。我们通过计算机数学模拟分析了该模型，并通过操作斑马鱼胚胎对其进行了检查。我们的跨学科方法揭示了形状依赖性随机不对称细胞分裂的设计原理。