Follow-the-leader cell migration requires biased cell-cell contact and local microenvironmental signals.
Follow-the-leader cell migration requires biased cell-cell contact and local microenvironmental signals.
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DOI：
10.1088/1478-3975/10/3/035003
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发表时间：
2013-06
期刊：
影响因子：
2
通讯作者：
Kulesa PM
中科院分区：
文献类型：
--
作者：
Wynn ML;Rupp P;Trainor PA;Schnell S;Kulesa PM
定向细胞迁移通常涉及至少两种类型的细胞运动，包括多细胞流和链式迁移。然而，尚不清楚的是细胞接触动力学和细胞移动的不同微环境如何影响一种或另一种迁移模式的选择。胚胎和高度侵入性神经嵴（NC）是研究这一问题的一个很好的模型系统，因为在体内观察到NC细胞表现出这两种类型的细胞运动。在这里，我们展示了小鸡组织移植实验和计算机模拟的数据，这些数据验证了我们的假设，即细胞之间的接触动力学和微环境促进和维持多细胞流或链式迁移。我们发现，当预迁移的颅NC细胞（在发育前水平）被移植到头部的一个更尾端的区域（在发育后水平）时，细胞改变了它们的特征流行为，并在链中迁移。同样，出生后的NC细胞在移植到出生前的后脑后也会成群迁移，这表明局部微环境信号决定了NC细胞的迁移模式。集成NC细胞行为数据的基于agent的模型（ABM）的模拟预测，链迁移严重依赖于有偏的细胞-细胞接触和局部微环境信号的相互作用。总之，这种集成的建模和实验方法提出了新的实验，并提供了一个强大的工具来检查复杂细胞迁移模式背后的机制。
Directed cell migration often involves at least two types of cell motility that include multicellular streaming and chain migration. However, what is unclear is how cell contact dynamics and the distinct microenvironments through which cells travel influence the selection of one migratory mode or the other. The embryonic and highly invasive neural crest (NC) are an excellent model system to study this question since NC cells have been observed in vivo to display both of these types of cell motility. Here, we present data from tissue transplantation experiments in chick and in silico modeling that test our hypothesis that cell contact dynamics with each other and the microenvironment promote and sustain either multicellular stream or chain migration. We show that when premigratory cranial NC cells (at the pre-otic level) are transplanted into a more caudal region in the head (at the post-otic level), cells alter their characteristic stream behavior and migrate in chains. Similarly, post-otic NC cells migrate in streams after transplantation into the pre-otic hindbrain, suggesting that local microenvironmental signals dictate the mode of NC cell migration. Simulations of an agent based model (ABM) that integrates the NC cell behavioral data predict that chain migration critically depends on the interplay of biased cell-cell contact and local microenvironment signals. Together, this integrated modeling and experimental approach suggests new experiments and offers a powerful tool to examine mechanisms that underlie complex cell migration patterns.