Purice Maria D, Ray Arpita, Münzel Eva Jolanda, Pope Bernard J, Park Daniel J, Speese Sean D, Logan Mary A
Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health and Science University, Portland, United States.
Melbourne Informatics, The University of Melbourne, Melbourne, Australia.
Elife. 2017 Aug 21;6:e23611. doi: 10.7554/eLife.23611.
Neural injury triggers swift responses from glia, including glial migration and phagocytic clearance of damaged neurons. The transcriptional programs governing these complex innate glial immune responses are still unclear. Here, we describe a novel injury assay in adult that elicits widespread glial responses in the ventral nerve cord (VNC). We profiled injury-induced changes in VNC gene expression by RNA sequencing (RNA-seq) and found that responsive genes fall into diverse signaling classes. One factor, matrix metalloproteinase-1 (MMP-1), is induced in ensheathing glia responding to severed axons. Interestingly, glial induction of MMP-1 requires the highly conserved engulfment receptor Draper, as well as AP-1 and STAT92E. In MMP-1 depleted flies, glia do not properly infiltrate neuropil regions after axotomy and, as a consequence, fail to clear degenerating axonal debris. This work identifies Draper-dependent activation of MMP-1 as a novel cascade required for proper glial clearance of severed axons.
神经损伤会引发神经胶质细胞的快速反应，包括神经胶质细胞迁移以及对受损神经元的吞噬清除。然而，调控这些复杂的先天性神经胶质免疫反应的转录程序仍不清楚。在此，我们描述了一种在成年果蝇中进行的新型损伤检测方法，该方法可在腹神经索（VNC）中引发广泛的神经胶质反应。我们通过RNA测序（RNA-seq）分析了VNC基因表达中损伤诱导的变化，发现反应性基因属于不同的信号类别。其中一个因子，基质金属蛋白酶-1（MMP-1），在对切断轴突作出反应的包被神经胶质细胞中被诱导表达。有趣的是，神经胶质细胞对MMP-1的诱导需要高度保守的吞噬受体Draper以及AP-1和STAT92E。在MMP-1缺失的果蝇中，神经胶质细胞在轴突切断后不能正常侵入神经纤维区域，因此无法清除退化的轴突碎片。这项研究确定了Draper依赖的MMP-1激活是神经胶质细胞正确清除切断轴突所需的一种新型级联反应。
