Modeling and Inferring Cleavage Patterns in Proliferating Epithelia
Modeling and Inferring Cleavage Patterns in Proliferating Epithelia
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DOI：
10.1371/journal.pcbi.1000412
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发表时间：
2009-06-01
影响因子：
4.3
通讯作者：
Nagpal, Radhika
中科院分区：
文献类型：
--
作者：
Patel, Ankit B.;Gibson, William T.;Nagpal, Radhika
卵裂面方向的调控是上皮细胞形态发生的关键机制之一。尽管如此，局部卵裂模式和组织水平特性之间的关系的许多方面仍然知之甚少。在这里，我们开发了一个拓扑模型，模拟动态的2D增殖上皮细胞从一代到一代，使各种各样的生物学合理的分裂模式的探索。我们调查了一系列的模型，将相邻细胞的空间影响和时间上的母细胞的选择上的分裂平面的影响。我们的研究结果表明，卵裂模式产生“签名”的多边形细胞形状的平衡分布。这些签名使局部卵裂参数的推断，如邻居的影响，母亲的影响，和分裂对称性从全球观察细胞形状的分布。将这些见解应用于五种不同生物体的增殖上皮细胞，我们发现，需要强大的分裂对称性和适度的邻居/母亲的影响，以再现六边形细胞的优势和经验上看到的细胞形状的低变异性。此外，我们提出了两个不同的卵裂模式模型，一个随机和一个确定性，可以重现经验分布的细胞形状。虽然五种不同生物的增殖上皮细胞显示出高度保守的细胞形状分布，但有多种可能的分裂模式可以产生这种分布，实验证据表明，植物和果蝇确实使用不同的分裂机制。
The regulation of cleavage plane orientation is one of the key mechanisms driving epithelial morphogenesis. Still, many aspects of the relationship between local cleavage patterns and tissue-level properties remain poorly understood. Here we develop a topological model that simulates the dynamics of a 2D proliferating epithelium from generation to generation, enabling the exploration of a wide variety of biologically plausible cleavage patterns. We investigate a spectrum of models that incorporate the spatial impact of neighboring cells and the temporal influence of parent cells on the choice of cleavage plane. Our findings show that cleavage patterns generate "signature" equilibrium distributions of polygonal cell shapes. These signatures enable the inference of local cleavage parameters such as neighbor impact, maternal influence, and division symmetry from global observations of the distribution of cell shape. Applying these insights to the proliferating epithelia of five diverse organisms, we find that strong division symmetry and moderate neighbor/maternal influence are required to reproduce the predominance of hexagonal cells and low variability in cell shape seen empirically. Furthermore, we present two distinct cleavage pattern models, one stochastic and one deterministic, that can reproduce the empirical distribution of cell shapes. Although the proliferating epithelia of the five diverse organisms show a highly conserved cell shape distribution, there are multiple plausible cleavage patterns that can generate this distribution, and experimental evidence suggests that indeed plants and fruitflies use distinct division mechanisms.