A novel injury paradigm in the central nervous system of adult Drosophila: molecular, cellular and functional aspects

被引:5
作者
Losada-Perez, Maria [1 ]
Garcia-Guillen, Nuria [1 ]
Casas-Tinto, Sergio [1 ]
机构
[1] Inst Cajal CSIC, Dept Mol Cellular & Dev Neurobiol, Madrid 28002, Spain
关键词
JNK; Macrophages; CNS damage; Glia; Immune response; Regeneration; GLIAL ENGULFMENT ACTIVITY; AXON REGENERATION; DRAPER; CELLS; GENES; PHAGOCYTOSIS; RECEPTOR; KINASE; REPAIR; EIGER;
D O I
10.1242/dmm.044669
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The mammalian central nervous system (CNS) exhibits limited regenerativ e capacity and the mechanisms that mediate its regeneration are not fully understood. Here, we present a novel experimental design to damage the CNS by using a contusion injury paradigm. The design of this protocol allows the study of long-term and short-term cellular responses, including those of the CNS and the immune system, and of any implications regarding functional recovery. We demonstrate for the first time that adult Drosophila melanogaster glial cells undergo spontaneous functional recover y following crush injury. This crush injury leads to an intermediate level of functional recovery after damage, which is ideal to screen for genes that facilitate or prevent the regeneration process. Here, we validate this model and analyse the immune responses of glial cells as a central regulator of functional regeneration. Additionally, we demonstrate that glial cells and macrophages contribute to functional regeneration through mechanisms involving the Jun N-terminal kinase (JNK) pathway and the Drosophila protein Draper (Drpr), characteristic of other neural injury paradigms. We show that macrophages are recruited to the injury site and are required for functional recovery. Further, we show that the proteins Grindelwald and Drpr in Drosophila glial cells mediate activation of JNK, and that expression of drpr is dependent on JNK activation. Finally, we link neuron-glial communication and the requirement of neuronal vesicular transport to regulation of the JNK pathway and functional recovery. This article has an associated First Person interview with the first author of the paper.
引用
收藏
页数:14
相关论文
共 93 条
  • [81] Heterodimers of NF-κB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila
    Tanji, Takahiro
    Yun, Eun-Young
    Ip, Y. Tony
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (33) : 14715 - 14720
  • [82] Three distinct stages of apoptotic nuclear condensation revealed by time-lapse imaging, biochemical and electron microscopy analysis of cell-free apoptosis
    Tone, Shigenobu
    Sugimoto, Kenji
    Tanda, Kazue
    Suda, Taiji
    Uehira, Kenzo
    Kanouchi, Hiroaki
    Samejima, Kumiko
    Minatogawa, Yohsuke
    Earnshaw, William C.
    [J]. EXPERIMENTAL CELL RESEARCH, 2007, 313 (16) : 3635 - 3644
  • [83] TREHERNE JE, 1984, J NEUROSCI, V4, P2689
  • [84] Analysis of the Trajectory of Drosophila melanogaster in a Circular Open Field Arena
    Valente, Dan
    Golani, Ilan
    Mitra, Partha P.
    [J]. PLOS ONE, 2007, 2 (10):
  • [85] Predetermined embryonic glial cells form the distinct glial sheaths of the Drosophila peripheral nervous system
    von Hilchen, Christian M.
    Bustos, Alvaro E.
    Giangrande, Angela
    Technau, Gerhard M.
    Altenhein, Benjamin
    [J]. DEVELOPMENT, 2013, 140 (17): : 3657 - 3668
  • [86] A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway
    Wendler, Franz
    Gillingham, Alison K.
    Sinka, Rita
    Rosa-Ferreira, Claudia
    Gordon, David E.
    Franch-Marro, Xavier
    Peden, Andrew A.
    Vincent, Jean-Paul
    Munro, Sean
    [J]. EMBO JOURNAL, 2010, 29 (02) : 304 - 314
  • [87] An Intrinsic Epigenetic Barrier for Functional Axon Regeneration
    Weng, Yi-Lan
    An, Ran
    Cassin, Jessica
    Joseph, Jessica
    Mi, Ruifa
    Wang, Chen
    Zhong, Chun
    Jin, Seung-Gi
    Pfeifer, Gerd P.
    Bellacosa, Alfonso
    Dong, Xinzhong
    Hoke, Ahmet
    He, Zhigang
    Song, Hongjun
    Ming, Guo-li
    [J]. NEURON, 2017, 94 (02) : 337 - +
  • [88] Regulation of wound healing by growth factors and cytokines
    Werner, S
    Grose, R
    [J]. PHYSIOLOGICAL REVIEWS, 2003, 83 (03) : 835 - 870
  • [89] The JNK signal transduction pathway
    Weston, Claire R.
    Davis, Roger J.
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2007, 19 (02) : 142 - 149
  • [90] Snail modulates JNK-mediated cell death in Drosophila
    Wu, Chenxi
    Li, Zhuojie
    Ding, Xiang
    Guo, Xiaowei
    Sun, Ying
    Wang, Xingjun
    Hu, Yujia
    Li, Tongtong
    La, Xiaojin
    Li, Jianing
    Li, Ji-an
    Li, Wenzhe
    Xue, Lei
    [J]. CELL DEATH & DISEASE, 2019, 10 (12)