Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.
Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.
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DOI：
10.1038/nature25742
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发表时间：
2018-02-22
期刊：
影响因子：
64.8
通讯作者：
Mayor R
中科院分区：
文献类型：
--
作者：
Barriga EH;Franze K;Charras G;Mayor R
集体细胞迁移(CCM)在形态发生、组织重建和肿瘤侵袭过程中起重要作用。在体内，成群的细胞在组织中以一种有组织的方式移动。这种运动需要作用力，并涉及细胞与其环境之间的机械和分子相互作用。虽然分子信号在CCM中的作用已被较好地了解，但组织力学如何在活体中影响CCM仍不清楚。在这里，我们研究了机械线索在非洲爪哇神经脊细胞集体迁移中的重要性，非洲爪哇神经脊细胞是一种胚胎细胞，其迁移行为被比作癌症侵袭。我们发现，在形态发生过程中，头神经脊下的头部中胚层变硬。这种僵硬启动了神经脊细胞从上皮到间充质的转变(EMT)，并触发了它们的集体迁移。为了检测其机械环境的变化，神经脊使用整合素/纽蛋白/Talin介导的机械传感。通过进行机械和分子操作，我们证明了中胚层硬化是触发神经脊迁移的必要条件和充分条件。最后，我们证明了在原肠形成期间开始的中胚层的会聚伸展，通过增加神经脊下的细胞密度而导致中胚层硬度的增加。这些结果揭示了中胚层会聚延伸作为形态发生的机械协调者的新角色，从而揭示了两个明显不相关的过程之间的新联系，即原肠形成和神经脊迁移，通过组织力学的变化。总体而言，我们提供了第一个证据，证明基质硬度的变化可以通过促进体内EMT来触发CCM。更广泛地说，我们的结果提出了一个令人兴奋的想法，即组织力学与分子效应器相结合来协调形态发生。
Collective cell migration (CCM) is essential for morphogenesis, tissue remodelling, and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement requires forces and involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in CCM is comparatively well understood, how tissue mechanics influence CCM in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion. We found that, during morphogenesis, the head mesoderm underlying the cephalic neural crest stiffens. This stiffening initiated an epithelial-to-mesenchymal transition (EMT) in neural crest cells and triggered their collective migration. To detect changes in their mechanical environment, neural crest use integrin/vinculin/talin-mediated mechanosensing. By performing mechanical and molecular manipulations, we showed that mesoderm stiffening is necessary and sufficient to trigger neural crest migration. Finally, we demonstrated that convergent extension of the mesoderm, which starts during gastrulation, leads to increased mesoderm stiffness by increasing the cell density underneath the neural crest. These results unveil a novel role for mesodermal convergent extension as a mechanical coordinator of morphogenesis, and thus reveal a new link between two apparently unconnected processes, gastrulation and neural crest migration, via changes in tissue mechanics. Overall, we provide the first demonstration that changes in substrate stiffness can trigger CCM by promoting EMT in vivo. More broadly, our results raise the exciting idea that tissue mechanics combines with molecular effectors to coordinate morphogenesis.
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影响因子：
25
作者：
Koser DE;Thompson AJ;Foster SK;Dwivedy A;Pillai EK;Sheridan GK;Svoboda H;Viana M;Costa LD;Guck J;Holt CE;Franze K
通讯作者：
Franze K
影响因子：
16.6
作者：
Moeendarbary E;Weber IP;Sheridan GK;Koser DE;Soleman S;Haenzi B;Bradbury EJ;Fawcett J;Franze K
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Franze K
影响因子：
11.8
作者：
Theveneau, Eric;Marchant, Lorena;Kuriyama, Sei;Gull, Mazhar;Moepps, Barbara;Parsons, Maddy;Mayor, Roberto
通讯作者：
Mayor, Roberto
影响因子：
21.3
作者：
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通讯作者：
Lenne, Pierre-Francois
影响因子：
64.8
作者：
Storm, C;Pastore, JJ;Janmey, PA
通讯作者：
Janmey, PA