Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada; Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, University of Toronto, Toronto, ON M5G 1M1, Canada.
Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.
Dev Cell. 2018 Nov 5;47(3):377-387.e4. doi: 10.1016/j.devcel.2018.10.013.
Embryos have a striking ability to heal wounds rapidly and without scarring. Embryonic wound repair is a conserved process, driven by polarization of cell-cell junctions and the actomyosin cytoskeleton in the cells around the wound. However, the upstream signals that trigger cell polarization around wounds are unknown. We used quantitative in vivo microscopy in Drosophila and zebrafish embryos to identify reactive oxygen species (ROS) as a critical signal that orchestrates cell polarity around wounds. ROS promote trafficking of adherens junctions and accumulation of actin and myosin at the wound edge and are necessary for wound closure. We show that, in Drosophila, ROS drive wound healing in part through an ortholog of Src kinase, Src42A, which we identify as a redox sensor that promotes polarization of junctions and the cytoskeleton around wounds. We propose that ROS are a reparative signal that drives rapid embryonic wound healing in vertebrate and invertebrate species.
胚胎具有快速愈合伤口而不留疤痕的惊人能力。胚胎伤口修复是一个保守的过程,由细胞连接处的极化和伤口周围细胞中的肌动球蛋白细胞骨架驱动。然而,触发伤口周围细胞极化的上游信号尚不清楚。我们使用定量活体显微镜在果蝇和斑马鱼胚胎中鉴定活性氧 (ROS) 作为一种关键信号,协调伤口周围的细胞极性。ROS 促进黏附连接的运输,并在伤口边缘积累肌动蛋白和肌球蛋白,这对于伤口闭合是必要的。我们表明,在果蝇中,ROS 通过 Src 激酶的同源物 Src42A 部分驱动伤口愈合,我们将其鉴定为一种氧化还原传感器,可促进连接和伤口周围细胞骨架的极化。我们提出 ROS 是一种修复信号,可驱动脊椎动物和无脊椎动物物种的快速胚胎伤口愈合。