Regulation by a TGFβ-ROCK-actomyosin axis secures a non-linear lumen expansion that is essential for tubulogenesis
Regulation by a TGFβ-ROCK-actomyosin axis secures a non-linear lumen expansion that is essential for tubulogenesis
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DOI：
10.1242/dev.117150
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发表时间：
2015-05-01
期刊：
影响因子：
4.6
通讯作者：
Jiang, Di
中科院分区：
文献类型：
--
作者：
Denker, Elsa;Sehring, Ivonne M.;Jiang, Di
管腔生长的调节对于确保管状结构的正确形态、尺寸和功能至关重要。对于这种情况是如何控制的，人们仍然知之甚少。在肠鞘脊索小管发生过程中，单个细胞外腔在细胞对之间生长，最终融合成一个连续的管子。在这里，我们发现管腔生长呈现滞后期，在此期间，管腔膜继续生长，但顶端/侧交界处的扩张暂停了大约30分钟。抑制非肌肉肌球蛋白II的活性可以消除这一滞后期，加速连接的扩张，导致形成较窄的管腔，部分融合成一个尺寸较小的管子。相反，肌动蛋白动力学的破坏会导致顶端/侧向连接扩张的逆转，导致细胞外管腔口袋戏剧性地转变为细胞内空泡，并导致小管形成停滞。延迟期的开始与肌动蛋白的从头积聚有关，肌动蛋白在顶端/侧端连接处形成一个收缩环。这种肌动蛋白环有效地限制了管腔在横向平面上的打开，使管腔有足够的时间通过沿纵向的渗透过程生长。管腔形成的动力学受转化生长因子β途径和岩石活动的控制。我们的发现揭示了一个协调管腔生长的转化生长因子β-岩石-肌动球蛋白收缩性轴，这是由管腔渗透压动力学驱动的。调节系统的功能可能像传感器/检查点一样，对管腔压力的变化做出反应，并微调肌球蛋白的收缩能力，以实现适当的小管形成。
Regulation of lumen growth is crucial to ensure the correct morphology, dimensions and function of a tubular structure. How this is controlled is still poorly understood. During Ciona intestinalis notochord tubulogenesis, single extracellular lumen pockets grow between pairs of cells and eventually fuse into a continuous tube. Here, we show that lumen growth exhibits a lag phase, during which the luminal membranes continue to grow but the expansion of the apical/lateral junction pauses for similar to 30 min. Inhibition of non-muscle myosin II activity abolishes this lag phase and accelerates expansion of the junction, resulting in the formation of narrower lumen pockets partially fusing into a tube of reduced size. Disruption of actin dynamics, conversely, causes a reversal of apical/lateral junction expansion, leading to a dramatic conversion of extracellular lumen pockets to intracellular vacuoles and a tubulogenesis arrest. The onset of the lag phase is correlated with a de novo accumulation of actin that forms a contractile ring at the apical/lateral junctions. This actin ring actively restricts the opening of the lumen in the transverse plane, allowing sufficient time for lumen growth via an osmotic process along the longitudinal dimension. The dynamics of lumen formation is controlled by the TGF beta pathway and ROCK activity. Our findings reveal a TGF beta-ROCK-actomyosin contractility axis that coordinates lumen growth, which is powered by the dynamics of luminal osmolarity. The regulatory system may function like a sensor/checkpoint that responds to the change of luminal pressure and fine-tunes actomyosin contractility to effect proper tubulogenesis.