Kathryn W. Davis Center for Regenerative Biology and Medicine, MDI Biological Laboratory, 159 Old Bar Harbor Rd, Bar Harbor, ME 04609, USA.
Kathryn W. Davis Center for Regenerative Biology and Medicine, MDI Biological Laboratory, 159 Old Bar Harbor Rd, Bar Harbor, ME 04609, USA
Development. 2019 Aug 2;146(15):dev173005. doi: 10.1242/dev.173005.
Tissue repair usually requires either polyploid cell growth or cell division, but the molecular mechanism promoting polyploidy and limiting cell division remains poorly understood. Here, we find that injury to the adult epithelium causes cells to enter the endocycle through the activation of Yorkie-dependent genes ( and ). Myc is even sufficient to induce the endocycle in the uninjured post-mitotic epithelium. As result, epithelial cells enter S phase but mitosis is blocked by inhibition of mitotic gene expression. The mitotic cell cycle program can be activated by simultaneously expressing the Cdc25-like phosphatase String (), while genetically depleting APC/C E3 ligase fizzy-related () However, forcing cells to undergo mitosis is detrimental to wound repair as the adult fly epithelium accumulates DNA damage, and mitotic errors ensue when cells are forced to proliferate. In conclusion, we find that wound-induced polyploidization enables tissue repair when cell division is not a viable option.
组织修复通常需要多倍体细胞生长或细胞分裂，但促进多倍体形成和限制细胞分裂的分子机制仍知之甚少。在这里，我们发现成年上皮组织受到损伤后，细胞通过激活依赖 Yorkie 的基因（和）进入内循环。Myc 甚至足以在未受伤的有丝分裂后上皮组织中诱导内循环。结果，上皮细胞进入 S 期，但有丝分裂被抑制有丝分裂基因表达所阻断。通过同时表达 Cdc25 样磷酸酶 String（），可以激活有丝分裂细胞周期程序，而遗传耗尽 APC/C E3 连接酶 fizzy-related () 然而，迫使细胞有丝分裂对伤口修复是有害的，因为成年果蝇上皮组织积累 DNA 损伤，当细胞被迫增殖时，有丝分裂错误就会发生。总之，我们发现，当细胞分裂不是可行选择时，伤口诱导的多倍体化可以促进组织修复。
