Shi Wenjie, Duclut Charlie, Xu Yan, Ma Yuanting, Qiao Jinghan, Lin Boyan, Yang Dongyu, Prost Jacques, Dong Bo
Fang Zongxi Center for Marine EvoDevo, Ministry of Education Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.
Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao 266237, China.
Proc Natl Acad Sci U S A. 2025 Jun 10;122(23):e2419960122. doi: 10.1073/pnas.2419960122. Epub 2025 Jun 5.
Interaction of cells and the surrounding lumen drives the formation of tubular system that plays the transport and exchange functions within an organism. The physical and biological mechanisms of lumen expansion have been explored. However, how cells communicate and coordinate with the surrounding lumen, leading to continuous tube expansion to a defined geometry, is crucial but remains elusive. In this study, we utilized the ascidian notochord tube as a model to address the underlying mechanisms. We first quantitatively measured and calculated the geometric parameters and found that tube expansion experienced three distinct phases. During the growth processes, we identified and experimentally demonstrated that both Rho GTPase Cdc42 signaling-mediated cell cortex distribution and the stability of tight junctions (TJs) were essential for lumen opening and tube expansion. Based on these experimental data, a conservation-laws-based tube expansion theory was developed, considering critical cell communication pathways, including secretory activity through vesicles, asymmetric cortex tension driven anisotropic lumen geometry, as well as the TJs gate barrier function. Moreover, by estimating the critical tube expansion parameters from experimental observation, we successfully predicted tube growth kinetics under different conditions through the combination of computational and experimental approaches, highlighting the coupling between actomyosin-based active mechanics and hydraulic processes. Taken together, our findings identify the critical cellular regulatory factors that drive the biological tube expansion and maintain its stability.
细胞与周围管腔的相互作用驱动了管状系统的形成，该系统在生物体内发挥着运输和交换功能。管腔扩张的物理和生物学机制已得到探索。然而，细胞如何与周围管腔进行通讯和协调，从而使管子持续扩张至特定几何形状，这一问题至关重要但仍不清楚。在本研究中，我们利用海鞘脊索管作为模型来探究其潜在机制。我们首先定量测量并计算了几何参数，发现管子扩张经历了三个不同阶段。在生长过程中，我们鉴定并通过实验证明，Rho GTP酶Cdc42信号介导的细胞皮层分布以及紧密连接（TJ）的稳定性对于管腔开放和管子扩张至关重要。基于这些实验数据，我们建立了一个基于守恒定律的管子扩张理论，该理论考虑了关键的细胞通讯途径，包括通过囊泡的分泌活动、由各向异性管腔几何形状驱动的不对称皮层张力以及TJ的门屏障功能。此外，通过从实验观察中估计关键的管子扩张参数，我们通过计算和实验方法的结合成功预测了不同条件下的管子生长动力学，突出了基于肌动球蛋白的主动力学与水力过程之间的耦合。综上所述，我们的研究结果确定了驱动生物管扩张并维持其稳定性的关键细胞调节因子。
