Laboratory for Histogenetic Dynamics, Department of Ecological Developmental Adaptability Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, 980-8578, Japan.
Laboratory for Histogenetic Dynamics, Department of Ecological Developmental Adaptability Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, 980-8578, Japan
Development. 2020 Apr 14;147(7):dev179648. doi: 10.1242/dev.179648.
Epithelial tissues undergo cell turnover both during development and for homeostatic maintenance. Cells that are no longer needed are quickly removed without compromising the barrier function of the tissue. During metamorphosis, insects undergo developmentally programmed tissue remodeling. However, the mechanisms that regulate this rapid tissue remodeling are not precisely understood. Here, we show that the temporal dynamics of endocytosis modulate physiological cell properties to prime larval epidermal cells for cell elimination. Endocytic activity gradually reduces as tissue remodeling progresses. This reduced endocytic activity accelerates cell elimination through the regulation of Myosin II subcellular reorganization, junctional E-cadherin levels, and caspase activation. Whereas the increased Myosin II dynamics accelerates cell elimination, E-cadherin plays a protective role against cell elimination. Reduced E-cadherin is involved in the amplification of caspase activation by forming a positive-feedback loop with caspase. These findings reveal the role of endocytosis in preventing cell elimination and in the cell-property switching initiated by the temporal dynamics of endocytic activity to achieve rapid cell elimination during tissue remodeling.
上皮组织在发育和维持稳态过程中都会经历细胞更新。不再需要的细胞会迅速被清除，而不会损害组织的屏障功能。在变态过程中，昆虫会经历发育编程的组织重塑。然而，调节这种快速组织重塑的机制尚不清楚。在这里，我们表明内吞作用的时间动态调节生理细胞特性，使幼虫表皮细胞为细胞消除做好准备。随着组织重塑的进行，内吞作用逐渐减少。这种减少的内吞作用通过调节肌球蛋白 II 亚细胞重排、连接 E-钙粘蛋白水平和半胱氨酸蛋白酶激活来加速细胞消除。虽然增加的肌球蛋白 II 动力学加速了细胞消除，但 E-钙粘蛋白通过与半胱氨酸蛋白酶形成正反馈环，起到了防止细胞消除的保护作用。E-钙粘蛋白的减少参与了半胱氨酸蛋白酶激活的放大，与半胱氨酸蛋白酶形成正反馈环。这些发现揭示了内吞作用在防止细胞消除以及内吞作用时间动态引发的细胞特性转换中的作用，以在组织重塑过程中实现快速细胞消除。
