Epithelial tubules form critical structures in lung, kidney, and vascular tissues. However, the processes that control their morphogenesis and physiological expansion and contraction are not well understood. Here we examine the dynamic remodeling of epithelial tubes in vivo using a novel model system: the extracorporeal vasculature of Botryllus schlosseri, in which the disruption of the basement membrane triggers rapid, massive vascular retraction without loss of barrier function. We developed and implemented 3-D image analysis and virtual reconstruction tools to characterize the cellular morphology of the vascular wall in unmanipulated vessels and during retraction. In both control and regressed conditions, cells within the vascular wall were planar polarized, with an integrin- and curvature-dependent axial elongation of cells and a robust circumferential alignment of actin bundles. Surprisingly, we found no measurable differences in morphology between normal and retracting vessels under extracellular matrix (ECM) disruption. However, inhibition of integrin signaling through focal adhesion kinase inhibition caused disruption of cellular actin organization. Our results demonstrate that epithelial tubes can maintain tissue organization even during extreme remodeling events, but that the robust response to mechanical signals-such as the response to loss of vascular tension after ECM disruption-requires functional force sensing machinery via integrin signaling.

中文翻译：

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使用3-D图像分析和虚拟重建功能来动态重塑血管组织的细胞架构。

上皮小管在肺，肾和血管组织中形成关键结构。但是，控制其形态发生以及生理性扩张和收缩的过程还没有被很好地理解。在这里，我们使用一种新型的模型系统：Botryllus schlosseri的体外脉管系统，研究了上皮管在体内的动态重塑，其中基底膜的破坏触发了快速，大量的血管收缩，而没有屏障功能的丧失。我们开发并实施了3D图像分析和虚拟重建工具，以表征未操纵血管和牵开血管壁的细胞形态。在对照和回归条件下，血管壁内的细胞都是平面极化的，具有完整的和依赖于曲率的细胞轴向伸长以及肌动蛋白束的牢固的周向排列。出人意料的是，我们发现在细胞外基质（ECM）破坏下正常血管和缩回血管之间在形态上没有可测量的差异。然而，通过粘着斑激酶抑制对整联蛋白信号的抑制引起细胞肌动蛋白组织的破坏。我们的研究结果表明，即使在极端的重塑事件中，上皮管也可以维持组织的组织，但是对机械信号（如ECM破裂后对血管张力丧失的反应）的鲁棒响应需要通过整联蛋白信号传导的功能力传感机制。我们发现在细胞外基质（ECM）破坏下正常血管和缩回血管之间在形态上没有可测量的差异。然而，通过粘着斑激酶抑制对整联蛋白信号的抑制引起细胞肌动蛋白组织的破坏。我们的研究结果表明，即使在极端的重塑事件中，上皮管也可以维持组织的组织，但是对机械信号（如ECM破裂后对血管张力丧失的反应）的鲁棒响应需要通过整联蛋白信号传导的功能力传感机制。我们发现在细胞外基质（ECM）破坏下正常血管和缩回血管之间在形态上没有可测量的差异。然而，通过粘着斑激酶抑制对整联蛋白信号的抑制引起细胞肌动蛋白组织的破坏。我们的研究结果表明，即使在极端的重塑事件中，上皮管也可以维持组织的组织，但是对机械信号（如ECM破裂后对血管张力丧失的反应）的鲁棒响应需要通过整联蛋白信号传导的功能力传感机制。