Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Kyoto, 606-8501, Japan.
Group of Genetics, Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8602, Japan.
Sci Rep. 2019 Dec 20;9(1):19549. doi: 10.1038/s41598-019-56137-z.
Multicellular organisms repair injured epithelium by evolutionarily conserved biological processes including activation of c-Jun N-terminal kinase (JNK) signaling. Here, we show in Drosophila imaginal epithelium that physical injury leads to the emergence of dying cells, which are extruded from the wounded tissue by JNK-induced Slit-Roundabout2 (Robo2) repulsive signaling. Reducing Slit-Robo2 signaling in the wounded tissue suppresses extrusion of dying cells and generates aberrant cells with highly upregulated growth factors Wingless (Wg) and Decapentaplegic (Dpp). The inappropriately elevated Wg and Dpp impairs wound repair, as halving one of these growth factor genes cancelled wound healing defects caused by Slit-Robo2 downregulation. Our data suggest that JNK-mediated Slit-Robo2 signaling contributes to epithelial wound repair by promoting extrusion of dying cells from the wounded tissue, which facilitates transient and appropriate induction of growth factors for proper wound healing.
多细胞生物通过进化保守的生物学过程来修复受损的上皮组织，包括激活 c-Jun N 端激酶（JNK）信号通路。在这里，我们在果蝇的 imaginal 上皮组织中表明，物理损伤会导致垂死的细胞出现，这些细胞通过 JNK 诱导的 Slit-Roundabout2（Robo2）排斥信号从受伤组织中挤出。减少受伤组织中的 Slit-Robo2 信号会抑制垂死细胞的挤出，并产生具有高度上调的生长因子 Wingless（Wg）和 Decapentaplegic（Dpp）的异常细胞。不适当的升高的 Wg 和 Dpp 会损害伤口修复，因为将这些生长因子基因中的一个减半可以消除 Slit-Robo2 下调引起的伤口愈合缺陷。我们的数据表明，JNK 介导的 Slit-Robo2 信号通过促进垂死细胞从受伤组织中挤出，从而促进适当的生长因子的短暂和适当诱导，有助于上皮伤口修复。
