In vivo topology converts competition for cell-matrix adhesion into directional migration
In vivo topology converts competition for cell-matrix adhesion into directional migration
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DOI：
10.1038/s41467-019-09548-5
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发表时间：
2019-04-03
影响因子：
16.6
通讯作者：
Theveneau, Eric
中科院分区：
文献类型：
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作者：
Bajanca, Fernanda;Gouignard, Nadege;Theveneau, Eric
当细胞在体内迁移时，暴露在许多相互矛盾的信号中：趋化因子、驱避剂、细胞外基质、生长因子。其中几个分子的作用已经在体外或体内进行了单独的研究，但我们还没有了解细胞如何整合它们。为了开始解决这个问题，我们使用了头神经脊作为一个模型系统，并观察了它的正负信号的最佳例子：基质细胞衍生因子1(SDF1/CXCL12)和class3-信号素。在这里，我们显示SDF1和Sema3A通过在单细胞水平上相反地影响rac1的活性来拮抗地控制细胞-基质黏附。种群水平的定向迁移是在偏向的纤维连接蛋白分布的背景下，由于全球对Semaphorin的依赖限制和SDF1对黏附的广泛激活而出现的。这些结果表明，体内不均匀的拓扑结构使得对分泌信号的精确分布的需求几乎是可有可无的。
When migrating in vivo, cells are exposed to numerous conflicting signals: chemokines, repellents, extracellular matrix, growth factors. The roles of several of these molecules have been studied individually in vitro or in vivo, but we have yet to understand how cells integrate them. To start addressing this question, we used the cephalic neural crest as a model system and looked at the roles of its best examples of positive and negative signals: stromal-cell derived factor 1 (Sdf1/Cxcl12) and class3-Semaphorins. Here we show that Sdf1 and Sema3A antagonistically control cell-matrix adhesion via opposite effects on Rac1 activity at the single cell level. Directional migration at the population level emerges as a result of global Semaphorin-dependent confinement and broad activation of adhesion by Sdf1 in the context of a biased Fibronectin distribution. These results indicate that uneven in vivo topology renders the need for precise distribution of secreted signals mostly dispensable.