Extracellular matrix stiffness cues junctional remodeling for 3D tissue elongation

Extracellular matrix stiffness cues junctional remodeling for 3D tissue elongation
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DOI:
10.1038/s41467-019-10874-x
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发表时间:
2019-07-26
影响因子:
16.6
通讯作者:
Bilder, David
Bilder, David
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chen, Dong-Yuan;Crest, Justin;Bilder, David

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器官是由细胞外以及细胞内在的力塑造而成的,但对于细胞群体动力学如何响应环境信号进行协调,人们知之甚少。在此,我们应用先进的图像分析技术来揭示细胞外基质响应性的细胞行为,这些行为驱动果蝇卵泡的伸长,果蝇卵泡是一个模型系统,其中基底膜的刚度指导三维组织形态发生。通过对野生型和圆卵突变体进行整体形态测量分析,我们发现适当的器官形状既不需要平均细胞形状的改变,也不需要定向的细胞分裂。相反,一个主要因素是卵泡前部细长细胞的重新定向。极化的重新定向受基底膜的机械信号调节,这些信号通过Src酪氨酸激酶转导,以改变连接性E - 钙黏蛋白的运输。这种对机械敏感的细胞行为代表了一种保守的机制,它可以在不同于使有边界的平面上皮伸长的过程中使无边缘的管状上皮伸长。
Organs are sculpted by extracellular as well as cell-intrinsic forces, but how collective cell dynamics are orchestrated in response to environmental cues is poorly understood. Here we apply advanced image analysis to reveal extracellular matrix-responsive cell behaviors that drive elongation of the Drosophila follicle, a model system in which basement membrane stiffness instructs three-dimensional tissue morphogenesis. Through in toto morphometric analyses of wild type and round egg mutants, we find that neither changes in average cell shape nor oriented cell division are required for appropriate organ shape. Instead, a major element is the reorientation of elongated cells at the follicle anterior. Polarized reorientation is regulated by mechanical cues from the basement membrane, which are transduced by the Src tyrosine kinase to alter junctional E-cadherin trafficking. This mechanosensitive cellular behavior represents a conserved mechanism that can elongate edgeless tubular epithelia in a process distinct from those that elongate bounded, planar epithelia.