Draper-mediated JNK signaling is required for glial phagocytosis of apoptotic neurons during Drosophila metamorphosis
Draper-mediated JNK signaling is required for glial phagocytosis of apoptotic neurons during Drosophila metamorphosis
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DOI：
10.1002/glia.23322
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发表时间：
2018-07-01
期刊：
影响因子：
6.2
通讯作者：
Kurant, Estee
中科院分区：
文献类型：
--
作者：
Hilu-Dadia, Reut;Hakim-Mishnaevski, Ketty;Kurant, Estee
中枢神经系统的发育涉及通过细胞凋亡和随后的吞噬作用消除多余的神经元。在果蝇中，这主要发生在三个发育阶段：胚胎发生，变态和新兴的成年人。两种跨膜胶质细胞吞噬受体，SIMU（哺乳动物稳定蛋白-2的同源物）和德雷珀（哺乳动物MEGF 10和Jedi的同源物），在胚胎发生期间介导凋亡神经元的胶质细胞吞噬。然而，很少有人知道在发展的后期阶段凋亡神经元的去除。在这里，我们表明，在变态过程中，德雷珀起着至关重要的作用，胶质细胞的凋亡细胞清除，而SIMU，这是主要表达在蛹巨噬细胞外的大脑，是不参与胶质细胞的吞噬作用。我们发现，德雷珀激活果蝇c-Jun N-末端激酶（dJNK）信号主要在成鞘胶质细胞和星形胶质细胞，在那里它是必需的有效去除凋亡神经元。我们的数据表明，除了dJNK通路，德雷珀还触发了一个额外的信号通路，能够消除蛹脑中的凋亡神经元。因此，这项研究表明，SIMU出乎意料地是不涉及在变态过程中的凋亡神经元的胶质细胞吞噬作用，并突出了新的作用，dJNK信号转导的发育凋亡细胞清除下游的德雷珀。
Development of the central nervous system involves elimination of superfluous neurons through apoptosis and subsequent phagocytosis. In Drosophila, this occurs mainly during three developmental stages: embryogenesis, metamorphosis and emerging adult. Two transmembrane glial phagocytic receptors, SIMU (homolog of the mammalian Stabilin-2) and Draper (homolog of the mammalian MEGF10 and Jedi), mediate glial phagocytosis of apoptotic neurons during embryogenesis. However, less is known about the removal of apoptotic neurons during later stages of development. Here we show that during metamorphosis, Draper plays a critical role in apoptotic cell clearance by glia, whereas SIMU, which is mostly expressed in pupal macrophages outside the brain, is not involved in glial phagocytosis. We found that Draper activates Drosophila c-Jun N-terminal kinase (dJNK) signaling predominantly in the ensheathing glia and astrocytes, where it is required for efficient removal of apoptotic neurons. Our data suggest that besides the dJNK pathway, Draper also triggers an additional signaling pathway capable of removing apoptotic neurons in the pupal brain. This study thus reveals that SIMU unexpectedly is not involved in glial phagocytosis of apoptotic neurons during metamorphosis and highlights the novel role of dJNK signaling in developmental apoptotic cell clearance downstream of Draper.