Department of Embryology, Carnegie Institution for Science, Howard Hughes Medical Institute, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Department of Pharmacology and Cancer Biology and Department of Cell Biology, Duke University Medical Center, C318 LSRC Box 3813, Durham, NC 27710, USA.
Curr Biol. 2013 Nov 18;23(22):2224-2232. doi: 10.1016/j.cub.2013.09.029. Epub 2013 Oct 31.
Reestablishing epithelial integrity and biosynthetic capacity is critically important following tissue damage. The adult Drosophila abdominal epithelium provides an attractive new system to address how postmitotic diploid cells contribute to repair.
Puncture wounds to the adult Drosophila epidermis close initially by forming a melanized scab. We found that epithelial cells near the wound site fuse to form a giant syncytium, which sends lamellae under the scab to re-epithelialize the damaged site. Other large cells arise more peripherally by initiating endocycles and becoming polyploid, or by cell fusion. Rac GTPase activity is needed for syncytium formation, while the Hippo signaling effector Yorkie modulates both polyploidization and cell fusion. Large cell formation is functionally important because when both polyploidization and fusion are blocked, wounds do not re-epithelialize.
Our observations indicate that cell mass lost upon wounding can be replaced by polyploidization instead of mitotic proliferation. We propose that large cells generated by polyploidization or cell fusion are essential because they are better able than diploid cells to mechanically stabilize wounds, especially those containing permanent acellular structures, such as scar tissue.
组织损伤后,重建上皮完整性和生物合成能力至关重要。成年果蝇的腹部上皮组织为解决有丝分裂后二倍体细胞如何参与修复提供了一个新的系统。
成年果蝇表皮的刺伤最初通过形成一个黑化的痂来闭合。我们发现,伤口附近的上皮细胞融合形成一个巨大的合胞体,该合胞体将薄片发送到痂下,以重新上皮化受损部位。其他较大的细胞通过启动内周期和多倍体化或通过细胞融合在更外围产生。Rac GTPase 活性对于合胞体的形成是必需的,而 Hippo 信号效应物 Yorkie 则调节多倍体化和细胞融合。大细胞的形成具有重要的功能意义,因为当多倍体化和融合都被阻断时,伤口不会重新上皮化。
我们的观察表明,伤口丢失的细胞质量可以通过多倍体化而不是有丝分裂增殖来替代。我们提出,通过多倍体化或细胞融合产生的大细胞是必不可少的,因为它们比二倍体细胞更能机械稳定伤口,特别是那些含有永久性无细胞结构的伤口,如疤痕组织。