Polarized microtubule dynamics directs cell mechanics and coordinates forces during epithelial morphogenesis
Polarized microtubule dynamics directs cell mechanics and coordinates forces during epithelial morphogenesis
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DOI：
10.1038/s41556-018-0193-1
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发表时间：
2018-10-01
影响因子：
21.3
通讯作者：
Matis, Maja
中科院分区：
文献类型：
--
作者：
Singh, Amrita;Saha, Tanumoy;Matis, Maja
细胞骨架结构的协调重排是控制细胞和组织形态发生的主要力量来源(1,2)。然而，与基于肌动蛋白的机械力不同，我们对源自其他细胞骨架成分的力的贡献的了解仍然很少。在这里，我们将微管建立为组织形态发生过程中细胞力学的核心组成部分。我们发现，在早期果蝇翼上皮发育过程中，单个细胞具有机械自主性。每个细胞都包含一个极化的顶端非中心体微管细胞骨架，该骨架承受压力，因此微管力的急剧消除会导致细胞缩短。我们进一步确定脂肪平面细胞极性 (Ft-PCP) 信号通路 (3,4) 在粘附连接 (AJ) 处耦合微管，并通过极化跨细胞稳定性在组织中形成基于微管的力，从而揭示了连接单细胞和组织力学的分子机制。总之，这些结果为解释微管的整体模式如何控制细胞力学以协调组织重塑过程中的集体细胞行为提供了物理基础。这些结果还为单细胞和组织水平上收缩性和突出性细胞骨架力的相互作用提供了替代范例。
Coordinated rearrangements of cytoskeletal structures are the principal source of forces that govern cell and tissue morphogenesis(1,2). However, unlike for actin-based mechanical forces, our knowledge about the contribution of forces originating from other cytoskeletal components remains scarce. Here, we establish microtubules as central components of cell mechanics during tissue morphogenesis. We find that individual cells are mechanically autonomous during early Drosophila wing epithelium development. Each cell contains a polarized apical non-centrosomal microtubule cytoskeleton that bears compressive forces, whereby acute elimination of microtubule-based forces leads to cell shortening. We further establish that the Fat planar cell polarity (Ft-PCP) signalling pathway(3,4) couples microtubules at adherens junctions (AJs) and patterns microtubule-based forces across a tissue via polarized transcellular stability, thus revealing a molecular mechanism bridging single cell and tissue mechanics. Together, these results provide a physical basis to explain how global patterning of microtubules controls cell mechanics to coordinate collective cell behaviour during tissue remodelling. These results also offer alternative paradigms towards the interplay of contractile and protrusive cytoskeletal forces at the single cell and tissue levels.