Department of Developmental and Stem Cell Biology, Institut Pasteur, CNRS UMR 3738, 25 rue du Dr. Roux, 75015 Paris, France.
Department of Computational Biology, Institut Pasteur, CNRS USR 3756, 28 rue du Dr. Roux, 75015 Paris, France.
Dev Cell. 2021 Jun 21;56(12):1700-1711.e8. doi: 10.1016/j.devcel.2021.05.006. Epub 2021 Jun 2.
What regulates the spatiotemporal distribution of cell elimination in tissues remains largely unknown. This is particularly relevant for epithelia with high rates of cell elimination where simultaneous death of neighboring cells could impair epithelial sealing. Here, using the Drosophila pupal notum (a single-layer epithelium) and a new optogenetic tool to trigger caspase activation and cell extrusion, we first showed that death of clusters of at least three cells impaired epithelial sealing; yet, such clusters were almost never observed in vivo. Accordingly, statistical analysis and simulations of cell death distribution highlighted a transient and local protective phase occurring near every cell death. This protection is driven by a transient activation of ERK in cells neighboring extruding cells, which inhibits caspase activation and prevents elimination of cells in clusters. This suggests that the robustness of epithelia with high rates of cell elimination is an emerging property of local ERK feedback.
什么因素调节组织中细胞消除的时空分布在很大程度上仍是未知的。这对于具有高细胞消除率的上皮组织尤其重要，因为相邻细胞的同时死亡可能会损害上皮的密封。在这里，我们使用果蝇蛹的背板（单层上皮组织）和一种新的光遗传学工具来触发半胱天冬酶的激活和细胞外排，首先表明至少三个细胞簇的死亡会损害上皮的密封；然而，在体内几乎从未观察到这种细胞簇。因此，细胞死亡分布的统计分析和模拟突出了一个发生在每个细胞死亡附近的短暂和局部保护阶段。这种保护是由邻近外排细胞的细胞中 ERK 的短暂激活驱动的，它抑制半胱天冬酶的激活，防止细胞簇中的细胞被消除。这表明，具有高细胞消除率的上皮组织的稳健性是局部 ERK 反馈的一个新兴特性。
