YAP is essential for tissue tension to ensure vertebrate 3D body shape.
YAP is essential for tissue tension to ensure vertebrate 3D body shape.
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DOI：
10.1038/nature14215
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发表时间：
2015-05-14
期刊：
影响因子：
64.8
通讯作者：
Furutani-Seiki M
中科院分区：
文献类型：
--
作者：
Porazinski S;Wang H;Asaoka Y;Behrndt M;Miyamoto T;Morita H;Hata S;Sasaki T;Krens SFG;Osada Y;Asaka S;Momoi A;Linton S;Miesfeld JB;Link BA;Senga T;Shimizu N;Nagase H;Matsuura S;Bagby S;Kondoh H;Nishina H;Heisenberg CP;Furutani-Seiki M
脊椎动物具有独特的3D身体形状，其中正确的组织和器官形状和对齐对于功能至关重要。例如，视力要求透镜以眼杯为中心，而眼杯又必须正确地定位在头部中。组织形态发生取决于力的产生、力通过组织的传递以及组织和细胞外基质对力的响应。尽管世纪前达西·汤普森（D'Arcy Thompson）假设陆地动物的体型是由重力决定的，但一直没有动物模型直接证明上述机械形态发生过程是如何协调的，以产生能够承受重力的体型。在这里，我们报告了一个独特的青鳉鱼（Oryzias latipes）的突变，hirame（hir），这是敏感的重力变形。hirembryos显示一个显着扁平的身体所造成的突变的雅普，核执行器的河马信号，调节器官的大小。我们发现，肌动球蛋白介导的组织张力减少胚胎，导致组织扁平化和组织错位，这两者都有助于身体扁平化。通过分析雅普在人细胞三维球体中的功能，我们鉴定了Rho GT3激活蛋白ARHGAP 18作为雅普在控制组织张力中的效应物。总之，这些发现揭示了雅普在调节组织形状和正确的3D身体形状所需的对齐方面的先前未被认识的功能。了解雅普的这种形态发生功能可以促进胚胎干细胞的使用，以产生需要多个组织正确排列的复杂器官。
Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force,. Although a century ago D’Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant,hirame(hir), which is sensitive to deformation by gravity.hirembryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced inhirembryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues.